Suggestions for Modernization of Indian Drugs and Cosmetics Act and Rules

 

                                                      - Ganadhish Kamat

Background

Drug regulatory system in India is governed by both Centre and State Governments under the Drugs & Cosmetics Act 1940 & Rules 1945 there under. As the dates in the title signify: the Act and the rules were enacted prior to independence when the drug development and manufacturing in India was in its infancy. Import was the main source of modern medicines and export was non-existent. Knowledge about Pharmaceutical science was also limited in pre independence days. All these are getting reflected in the way the Act and rules have been framed.

During past one decade, India has become a major global supplier for both Active Ingredients (APIs) as well as finished dosage forms supplying high quality drugs to countries all over the globe. In fact, India has more USFDA approved manufacturing facilities outside USA and supplies almost 40% of generic products to USA. Availability of knowledgeable workforce and low cost manufacturing base, has helped India to become a global supplier of high quality pharmaceutical products all over the world. This has not only helped in reducing healthcare costs of countries across the globe but also helped Pharmaceutical companies in India to grow. This has become possible due to Pharmaceutical companies adapting to the requirement & expectation of international regulatory guidelines by upgrading the facilities, quality systems as well as imparting necessary training to the people.

Indian pharmaceutical companies with global presence have successfully adopted and implemented cGMP and other regulatory requirements of India along with this of other major regulatory authorities like USFDA, MHRA, TGA etc. which have been largely harmonized due to efforts by bodies like ICH, PICS and WHO. Indian drug laws in contrast have not kept pace with the developments across the globe which deprives Indian consumers of same quality standards of medicines which are available in advanced countries. The act and the rules are largely focused on administrative controls through licensing and surveillance through inspections, sampling, and testing. Many of the regulations have become outdated in light of new developments in the pharmaceutical science and some create hindrance in innovation and drug development. Time has come for complete overhaul of the D&C Act and the Rules to make it more efficient and effective in ensuring quality and safety of the drugs in India and while removing unnecessary burden on manufacturers and the enforcement agency.

Improvements required in D&C act 1940

FDA organization

Currently FDA has apex body known as Central Drug Standards Control Organization (CDSCO) headed by Drug Controller General of India (DCGI) with 4 regional offices for each of North Zone (Ghaziabad), West Zone (Mumbai), South Zone (Chennai) and East Zone (Kolkata). In addition, there are sub-zonal offices located at Hyderabad and Ahmedabad. CDSCO comes under the ministry of Health and Family welfare of the Central government with DCGI reporting to Secretary of the Health ministry. Each state has State FDA bodies headed by Drug controllers / Commissioners. The State FDA comes under Health and Family welfare ministry of the State government. Broadly Central organization is responsible for policy decisions, permission for new drug trials including clinical trials, approval of new drugs, monitoring of Adverse drug events and taking appropriate actions, grant of COPPs etc.  State FDAs are responsible for grant of manufacturing and sales and distribution licenses, periodic audits, collection of samples, enforcement actions etc. There is no direct control of the Central Drug control organization on the State drug control organizations. This makes it difficult to uniformly implement the policies' and standards across the states. Since both the Central and the State drug control organizations are subservient to the respective ministries, there is often political interference in the technical decisions. Since the decisions taken by the Central and the State Drug control organizations are required to be based on technical data, these organizations should be independent of any political interference. The position of Head of the Central drug organization is very important and should be at the level of cabinet minister to ensure that there is adequate independence on decision making. State Drug control organizations should be under the Central organization so that all the policies and standards can be uniformly implemented across all the states. 

The D&C act has defined structure and responsibilities of Drugs Technical Advisory Board (DTAB), Central Drugs Laboratory (CDL) and Drugs Consultative Committee (DCC) but neither the act nor the rules clearly define the organizational structure and roles and responsibilities of Central and state organizations. The complete organization structure indicating various divisions etc. and roles and responsibilities should be made part of Act. Requirements like roles, responsibilities and activities of Inspector, Government analyst etc. should be covered under Organization.

Current regulations give excessive power to DTAB in framing and modifying the rules as well as in deciding all major issues. The composition of DTAB as defined in the act however does not include the right subject matter experts. There is very little representation from the industry although the industry today has maximum knowledge in the field. Some representatives like head of CDL, Head of PCI, representatives from certain pharmaceutical organization etc. have been included which is not logical in current scenario. This board should be eliminated, and the responsibility of any policy changes should be with CDSCO. To make the process effective and scientific, CDSCO organization need to be strengthened by inducting adequate people with right capabilities creating proper structure. Committees of relevant subject matter experts may be formed from time to time to provide advice to CDSCO on specific issues.

In absence of detailed guidelines and directives for various activities, different states follow different approaches for various activities including grant of product permissions.  In absence of clear guidelines, for many issues, permission is first required to be obtained from CDSCO. This results in too much of centralization and delays. To avoid this CDSCO should lay down very clear guidelines for all activities and delegate most activities to state FDAs

Drug approval process

Following changes are suggested to the new drug approval process:

Marketing Authorization

Currently state FDA grants product licenses to the manufacturers for allowing them to manufacture and market the products irrespective of country where the products are marketed. Manufacturing cannot be initiated unless such license is obtained. This often delays the launch of products in the foreign countries where Day 1 launches after patent expiry and after approval of application are critical. It is common practice in foreign countries to manufacture the product in anticipation of approval but distribution is allowed only after approval of the application. Similar approach should be adopted for marketing of drugs in India by granting “Marketing authorization” instead of current product permission. The Marketing authorization should have lifelong validity unless withdrawn by the Agency.

Indian regulatory agency should only review application for drugs to be marketed in India. There should be no restriction on manufacturing of products for export, as they are reviewed and approved by respective countries regulatory agency.

Application process

Application review and approval process should be centralized to ensure uniformity and consistency. For marketing any new drugs and any new combination of already approved drugs in India, the application shouldbe made to central organization. The application should be in CTD format (the draft guidance for which was already issued in 2010). This will enable harmonized process for evaluation of all drugs intended for Indian population and ensure better quality products in India. e-CTD filing process should be facilitated, where the complete application can be made through a portal and all submissions are done electronically. This will greatly enhance the efficiency and effectiveness of product approval process. This will help in better data archival and quick retrieval while simultaneously reducing usage of paper and reducing storage space. Access to the applications should be provided to CDL and state government testing laboratories, so that they can access the approved specifications and test procedures for testing of surveillance samples.

Clinical Data

For new drug products clinical study protocol shall be submitted for approval. Based on the nature of the product and therapeutic area, the number of subjects and the number of centers may be approved. Thefrequency of the technical committee which is responsible for approval shall be increased from once in 3 months to once in a month. This will greatly help the pharmaceutical industry to speed up the clinical trials for evaluating the safety and efficacy of drug in targeted population for the drug. This will also help in shrinking the time to bring the product to market.

Drug Application Review Process

Central organization should have application review division with adequate technically qualified resources to facilitate timely review and approval. Performance goals for drug approval process in terms of review time should be decided for predictable outcome of time for new products / generic product to reach to market.

The review may be divided into subdivisions like administrative review, manufacturing and clinical review of the submission with each of these portions reviewed by dedicated teams. Project management may be created with each submission given to a project manager, who will act as front end to coordinate with the concerned company for a speedy review and approval of dossier.

Drug Approval – Issuance of marketing authorization

Once the drug application is reviewed, then, a marketing authorization in the name of the company indicating the drug approved and any additional conditions for drug approval along with the manufacturing facility at which they are approved for manufacturing and marketing may be issued.

Changes to an approved application

Currently there is no system of approval of post approval changes. A formal process for approval of changes to an approved marketing authorization needs to be put in place. The changes may be classified as self-assessable changes and that require a formal approval from the regulatory authority. A guidance document on similar lines issued by USFDA for Scale Up and Post Approval Changes (SUPAC) and EU guidance on “Variations to an Approved Marketing Authorization” shall be brought about for reporting various categories of changes to the agency. This will ensure that all changes are properly reported and evaluated to ensure continued safety, quality and efficacy of drugs.

If the same product is manufactured at different manufacturing facilities located at different geographical locations, inclusion of multiple sites should be allowed in original approved marketing authorization. This will help not only faster approval, but also reduce a lot of duplication of assessing same product by different state authorities.

Generic Drug Approval

For generic products also application should be in CTD format. All sections of CTD should be applicable except Clinical Study Reports. BA/BE(Bioavailability/Bioequivalence) studies on healthy volunteers should be given instead of clinical data.

The responsibility for approval generic drugs may be kept with State drug control authority provided adequate review team is established for such activity. Alternatively, this responsibility can also remain with central agency. Incase the first option is chosen;State FDA should have access to data base of corresponding new drug (by innovator / first to file) which is approved by CDSCO through an electronic gateway. This will help in accessing the generic drug application vis-à-vis innovator.

Currently, conducting clinical studies is applicable to all potential entrants who submit application for marketing within 4 years of new drug / first time approval. After 4 years there is no requirement to conduct any BA/BE studies for subsequent applicants. The current system of approving generic products without BA/BE studies may lead to issues in both safety and efficacy. (BA/BE) studies should be made mandatory for all generic products that seek approval for marketing in India. This will ensure that only drugs with proven safety and efficacy reach patients leading to better healthcare outcomes. Similarly, the requirement for carrying out clinical study by all applicants within first 4 years should be eliminated as the 4 year term defined has no scientific rationale.

Procedure for approval of BE protocols should be scrapped instead a detail guideline for the BE studies should be established and responsibility of compliance should rest with the applicant.

The process for changes to an approved marketing authorization as described for new drugs should also be adopted for generic drugs.

Product licensing for export

For product meant only for export the licensing process should be significantly simplified as detail review is done by regulatory agency of the importing country. State licensing organization should issue license for manufacture only based on the evidence that application has been submitted in importing country.

The system for granting licenses for fixed quantity should be scrapped since products can only be exported they are registered in importing country. This will improve efficiency with which company can react to the product needs for export and reduce work at CDSCO and state FDA offices.

Test licenses

The test licensing process should be eliminated or only restricted to R&D centers. The time limit for such licenses to be removed. This will reduce the number of renewal application. There is no risk since the product manufactured is only for development purpose and not for consumption.

Structure & Approach of the Act

Sections need to be arranged in logical order and should be made more meaningful. Instead of just defining the powers and responsibilities of agencies, the act should describe the requirements which need to be complied under various activities described in different chapters. Since India now does significant Export, separate chapter should be introduced for Exports. This section should include procedure for grant of COPPs and Written confirmations for ensuring harmonized approach in each state. State FDA offices should be authorized to issue the written confirmations and COPPs to improve the speed and efficiency.

Devices and drug device combinations should be included. Sections like Standards of quality, Misbranded drugs, spurious drugs etc. are common for Import, manufacturing, distribution and exports. So, they need not be covered under each chapter but should be covered under definitions. Responsibilities of Government analyst, Inspectors etc. should not be repeated under each chapter but covered under organization. Major changes are required in the introductory section as many of the clauses are no longer applicable. Some of the definitions have to be changed in light of current understanding and global standards. Some new definitions like Drug substance, Drug product etc. need to be introduced in line with ICH& PICS guidelines.

Central Drug Laboratory

While it is required to have Government testing laboratories to monitor the quality of the drugs, having one Central Drug laboratory does not make sense when drugs are manufactured and distributed in such vast country. Transportation of samples from across the country under proper conditions to maintain their integrity could be big challenge and expensive too with single central laboratory. Each state should have fully equipped testing laboratories meeting global standards.

Import of drugs

Law should allow re-import of rejected batches (API) originally exported by the firm for the purpose of investigation, destruction, or re-processing without need for additional import license.

There should also be provision to allow import of small quantities of samples (complaint samples) for the investigation of any complaints related to exported drugs without need for taking any additional license or permission.

Import of innovator products for the purpose of testing, evaluation and BA/BE studies should be allowed in reasonable quantities without need for special permission or license. Requirements can be defined in the law to maintain proper records of such samples.

Manufacture Sales and Distribution

The chapter needs complete overhaul describing the conditions which manufacturer and distributer need to follow instead of just stating the prohibitions under law, procedures for inspectors, powers of the government etc. The procedures should be covered into separate manuals rather than the act itself as they are likely to get changed over period of time. Requirements related to Manufacture and Sales & distribution should be separated due to diverse agencies involved in these two separate activities.

Schedules to the Act

Both 1^st and 2^nd Schedule to the act should be removed. There is no reason for providing list of the books in the act. All the decisions, actions should be based on scientific rationale and in reference to latest literatures available rather than specific set of books. Similarly, the standards should be established based on scientific rationale to ensure efficacy and safety and should be filed in the application. This can be described in the definition itself instead of separate schedule. The standards defined in Pharmacopoeial monographs are minimum standards which the drugs need to meet.

Comments on Drugs and Cosmetics rules 1945

Definitions

Some of the definitions need to undergo change for example the term “Laboratory” should not be restricted to CDL. The definition should be broadened to include other government laboratories and also any future laboratories which may come in existence. There is no rationale for Phytopharmaceutical drug to have certain number of bioactive or phyto-chemical compounds. Some new definitions need to be incorporated as mentioned under the Act.

The Central Drugs Laboratory, collection of samples and their analysis

To ensure accuracy and reliability of the test results, it is very important that drug samples are stored and transported under right storage conditions as specified on the label. The rules currently does not have any control on this. It should be made mandatory that all the samples are handled (collection, transportation, storage)in a manner which maintain the integrity of the samples. Data loggers should accompany the samples to create evidence that the samples were transported under right condition. All places where the samples are stored (drug control offices, Government test laboratories, including CDL etc.) should have appropriate storage facilities to keep the drugs under right condition as specified on the label till they are analyzed. Record should be maintained that storage conditions were maintained as required.

The government testing laboratories including CDL should follow all the cGMP requirements like, traceability of standards, calibration of the laboratory instruments, manual and electronic data management including appropriate access and privilege controls, data security, data review, audit trail controls, laboratory incidences, OOS(out of specification) investigations etc. If the results of analysis are confirmed to be out of specification (OOS) after laboratory investigation, concerned manufacturer should be informed and given opportunity to carry out investigation and submit a complete response to FDA before initiating action. If necessitated, FDA should allow joint analysis when better understanding of method of analysis is required for arriving at right conclusion.

Any sampling of raw materials (including that of imported drugs) should be strictly done under appropriate controls of area classification, temperature and humidity controls etc. by taking all necessary precautions for preventing any contamination. Where material requires maintaining of inert atmosphere in the container, same should be done after sampling. Preferably all such sampling should be done in the manufacturing facility where such controls are available. Sampling of sterile materials should be avoided and if required should be done only in aseptic conditions (Grade A with grade B background on in isolator)

Import and Registration

Instead of controlling imports through import license, control should be exercised on distribution through Marketing authorization as mentioned earlier. This will ease importing of drugs for the purpose of development, testing, trials etc. If this is not possible, at least importation of small quantities for the purpose of examination, test or analysis should be permitted without license. Re-import of drugs exported by a company due reasons such as complaint investigations, stability studies, transportation studies, comparative evaluation, rejection by customer or return on commercial grounds should be allowed without need of separate import license.  Appropriate controls on the re-imported goods can be ensured through appropriate requirements in other chapters like Schedule M.

Conditions like adhering to appropriate storage condition is applicable for all the drugs and hence should be covered under separate section covering storage and transportation instead of under Imports. Clause of 60% residual shelf life should be removed as there is no problem as long as the goods are consumed within the shelf life. As new ports and airports may start handling international cargo, restriction for importing through specific ports or airports should be removed.

Government Analysts, Inspectors, Licensing Authorities & Controlling Authorities

Now a days there are many drugs in market for which Pharmacopeial standards don’t exist; in such case specifications and test methods need to be obtained from the drug control office holding the original application or from the manufacturer. Such provision needs to be included. As mentioned earlier access to dossier which contain all this information should be given to government analyst. Many current methods require reference standards / working standards, specific columns etc. which may not be available in the government test laboratory. In such cases, such materials are often obtained from the manufacturer. Provision for this should be made in the rules. Govt analyst should not be allowed to develop their own test methods as such activity requires detailed understanding of the formulation, impurity standards and extensive development work and method validation. As mentioned earlier, it is important to send the samples under appropriate conditions as mentioned on the label and maintaining appropriate storage conditions till testing is completed so that the integrity is maintained. Data loggers & other controls mentioned earlier should be used to ensure that the conditions are maintained.

Sale of Drugs

All the requirements related to sales and distribution should be brought under this section by separating out some sections related to sales under Part VII. It should be made mandatory that all premises (wholesale, C&F, retail) where the activities related to storage, sale and distribution are carried out, have adequate controls on temperature to allow storage of drugs under labeled storage condition. While some drugs are required to be stored below 25° C, 2 – 8° C etc. others which do not have specific storage conditions, should be stored at temperature not above 30° C as that has been accepted as long term storage condition for stability testing for drugs distributed in India. Appropriate controls are also required to be brought into the rules for transportation of medicines under right temperature conditions.

Where drug compounding and dispensing is performed in Pharmacies, it should be made mandatory that appropriate controls & hygienic conditions in line with Schedule M are maintained to avoid any contamination & cross contamination of drugs.

Requirements such as separate register for certain categories of drugs or maintaining carbon copies etc. should not be made mandatory as most establishments now use computerized systems with better controls. Exemptions for such manual records should be provided where alternate better controls are in place.

Manufacture for sale and distribution

Sale and distribution aspects including Prohibition of advertisement should be separated out from this section and merged under Sale of drugs. This section should exclusively describe the conditions and rules related to manufacture of drugs and associated activities.

As mentioned earlier, instead of manufacturing license for specific products, Marketing Authorization should be granted. Restriction on manufacture of drugs should be removed. General manufacturing license for certain categories of drugs or GMP certification of manufacturing site should be granted based on the inspection of facility and same should be renewed on periodic basis. There should be clarity about who will do this GMP certification (Central agency or state agency) so that there is no duplication of activity.

Need for having separate license for Schedule C & C1 from rest of the categories should be eliminated. License should be granted for different categories of the of the drugs provided necessary requirements for different categories as described in Schedule M are met. Marketing authorization should be independent of manufacturing sites. It should be allowed to include additional manufacturing sites including CMOs (Contract manufacturing organizations)in the authorization by submission of necessary information about manufacturing sites in the original application or supplemental application for post approval change. System for loan license should be scrapped and any CMO used to manufacture should be considered as additional site.

Requirement of competent technical staff should be removed. Having one such person does not serve the purpose. As per GMP requirements manufacturing unit should have adequate number of qualified personnel to perform various activities. All these people need to have adequate training to perform their activities.

Provision for outsourcing of certain tests to be modified to allow outsourcing of any test and not specific ones as mentioned in the rules. Outsourcing such activities to approved testing laboratory or another facility of same manufacturer should be allowed. This will help to have common testing facilities to be shared with multiple manufacturing facilities of same company either fully or for carrying out certain activities involving expensive techniques.

Use of electronic systems with appropriate controls should be allowed in lieu of bound books prescribed in current rules.

Prohibition for manufacture of Cyclamate is out of place in this section. First of all, it is not drug. It is an excipient which is banned in some countries. The use of Cyclamate in medicines can be prohibited. However, since there are many excipients which may fall in prohibited category, a list of such ingredients (including colors) can be provided in the Schedule. Cyclamate is not banned in some countries including Europe and manufacturing of the same for the purpose of export should be allowed.

Manufacture for Examination, Test or Analysis

Need for obtaining license for carrying out such activities should be eliminated to enable ease of new product development. The distribution of drugs in India should be controlled through Marketing authorization. Controls required for ensuring safety of commercial drugs manufactured in the same facility should be described under Schedule M.

Labeling and Packaging of the drugs

The requirements specified in this section should be applied only for drugs made for distribution in India and drugs manufactured for exports should be exempted from compliance to these requirements as manufacturers are required to adhere to individual countries requirements where the drugs are distributed. This change will eliminate hassles of obtaining various NOCs from DCGI and reduce work load of DCGI as well as companies.

Batch numbering

In continuous manufacturing, the production from defined period should be considered as one batch. Such portion can not be exactly called as homogenous mix because entire quantity is not mixed together. Since continuous manufacturing technology is becoming common now for both API and Drug product manufacturing, specific examples should be removed from the Rules. Restriction for 1 day for assigning batch number for aseptically filled product filled in one single operation should be removed. The run time of the batch should be restricted by longest run time established by media fill. On the contrary the same bulk filled aseptically in different filling operations should be given different batch number even if sample from each lot passes the sterility test because testing alone can not guarantee the quality.

Some specific labeling requirements

Changes are required with respect to following specific requirements mentioned in the rules

·        Schedule P should be eliminated as it is not scientific. Shelf life should be assigned based on the stability studies. Stability studies in line with ICH requirements should be made mandatory

·        Printing of red line does not provide any benefit and should be eliminated.

·        Instead of name of manufacturer, name of marketing authorization holder should be printed to allow use of same packaging inventory across multiple sites.

·        The pack sizes should be based on the stability studies and the dosage regimen of the drug. Restriction on certain sizes, multiple etc. should be removed from the rule. The pack sizes for individual drug should approved as part of marketing authorization based on the justification provided in the application.

·        The drug substances should be assigned re-test date instead of expiration date in line with global requirements. The re-test should be established based on the stability studies.

Special provisions relating biological and other special products

In the requirement for multidose injectable container, the word “Antiseptic” to be replaced by “Antimicrobial”.  Exemption should be given for multidose vaccine containers which are used withing short span of time from first use. Penicillin should not be considered as biologic. Term biologics should be used for large molecules. Specific drug requirements should be removed from the rules and general considerations should be included.

As the sterility test is described in IP and other Pharmacopoeias, there is no need to include this in the rules. Retesting should not be allowed in case of failure in initial sample unless the root cause is identified as laboratory error resulting in contamination of sample. Re-sterilization of failing batch should not be allowed. Test for Toxicity should be deleted and test for Pyrogens should be replaced by Endotoxin test. All injectables irrespective of volume should be tested for endotoxins.

Import or Manufacture of New drugs for clinical trials or marketing

There is no need to have separate section for fixed dose combination. Any such combination should be treated as drug and should follow same procedure for approval (i.e. safety and efficacy demonstrated by clinical studies or bio equivalence).4 year clause for considering the drug as new to be removed as there is no scientific rationale for it. Once a new drug is approved, subsequent approvals may be granted based on BA/BE data (provided there is no patent infringement).

Standards

These requirements should be applicable for only drugs distributed in India. Once new edition of Pharmacopoeia becomes effective, the old edition becomes obsolete. Reference to old edition should not be allowed. If the monographs has been dropped from IP for any reason, the drug should be allowed to be marketed as non-pharmacopoeial (P&P) drug unless there is safety issue. The list of permitted colors need to be updated based new safety information available.

Manufacture of Cosmetics for Sale or Distribution

Some of the changes suggested earlier for the Drugs are also applicable for cosmetics. They have not been repeated to avoid duplication.

Public testing laboratories

Manufacturers should be allowed to use testing facilities available at their own other sites (approved by agency) without need for any additional permission. Use of common testing facility set up to support multiple manufacturing sites should also be allowed after due inspection and approval by the authority.

Manufacture for sale of Ayurvedic, Siddha & Unani drugs

All marketing authorization for all kinds of medicines including Ayurvedic, Siddha, Unani etc should be granted strictly on the basis of safety and efficacy data. Appropriate standards and test methods should be made mandatory and testing should not be optional. Requirement of instrument should be based on the products analyzed in the lab and the tests conducted. The list should not be part of the rules. The shelf life should be based on stability testing (including microbial controls)

Schedules to Drugs and Cosmetics Rules

Many of the schedules have become redundant due to new developments/understanding in Pharmaceutical science and some need significant changes as described below.

Schedule A

All the forms should be made digital (electronic format). Some of the will become redundant after implementation of suggestions given earlier. After making the forms digital this schedule itself can be eliminated from the rules.

Schedule B

The fees prescribed in the schedule appear to be too less to even recover the cost of testing and maintenance of the lab in good order. Current analytical techniques like HPLC, GC, IR cost lot more due to cost of consumables like columns, reference standards, reagents etc. The costs need to be revised to make the laboratories self-sustaining.

Schedule C

Antibiotics, sterile products etc. need not be put into separate schedule. They should be treated like any other drugs (small molecules).

Schedule F(I), F(II) & F(III)

Instead of including standards& test methods for vaccines, surgical dressing and Umbilical tapes in the schedules to rules, it will be good to create separate compendia or include them in IP.

Schedule FF

No separate schedule is required to lay down requirement for ophthalmic products. Requirements in individual monograph and general monographs of Pharmacopoeia to be followed.

Schedule G, H & H1

Categorization of molecules under these schedules are not always scientific for example Metformin falls under Schedule G (drug to be taken under medical supervision) or Ibuprofen falls under schedule H (To be dispensed only against Prescription). These schedules should be eliminated. There should be only two categories of drugs, namely Prescription drugs which should be allowed to be dispensed only against prescription and OTC (Over the counter) drugs which can be sold over the counter. List of OTC medicines should be posted on the CDSCO website and periodically updated.

Schedule J

Treatments are now available for many of the ailments listed in this schedule. This schedule should be deleted. Any claim should be supported by clinical data which should be evaluated as part of drug product approval.

Schedule K

There is no need to provide such exceptions as specified in this schedule and hence this should be deleted.

Schedule L

In line with global standards, laboratory controls may be clubbed under Schedule M (Good manufacturing practices) because globally the term GLP is used in context of clinical studies.

Some of the requirements like need for logbooks etc. should not be made mandatory as newer technologies make them redundant and same controls can be achieved through automation and digitization. Provision for use of such laboratory automation in lieu of the manual records should be included.

Schedule M

Time has come for India to adopt International guidance for Good manufacturing practices for harmonization of Indian manufacturing in-line with global expectations.On formulation front, PICS guidelines for Good Manufacturing Practices (GMP) for manufacturing facilities. For active ingredient sites, ICH-Q7 may be adopted as basic guideline for GMP.Emphasis should be given on ensuring reliability of data submitted in drug applications and data of commercial batches by including clauses for control of paper and electronic data.

Some of the specific points which should be adopted in drug law are:

o   Allowing Reduced testing / skip testing for raw materials and packaging materials based on vendor’s quality system evaluation, controls at vendor’s end for ensuring consistent quality, rejection rate, transport validation etc. This will ensure elimination of duplication in testing.

o   Allowing digital controls in lieu of physical quarantines and color coded labels for identifying material status.

o   The carpet area required for different manufacturing suites and allied rooms shall be based on the size of operations, equipment installed and movement of men and material. Specific sizes mentioned as mandatory for these suites should be removed.

o   Requirement for Drug product shelf life to be lower than the shelf life of the API used in it should be eliminated as it is not scientific because the specification limits for the assay as well as related substances in API are much tighter as compared to drug product. Shelf life of the drug product should be established based on the stability studies.

Schedule N

The Pharmacies should have appropriate temperature controls and monitoring to ensure stability of the drugs. Since LT storage condition for India is 30°C, It should be made mandatory that temperature is controlled below that. Some medicines might have specific storage conditions like Store below 25°C, store at 2-8°C etc. There should be provision to store such drugs as per the storage condition defined on the label.

Schedule O

Such standards should be part of books of Standards like Pharmacopoeia or BIS and need not be included in Rules.

Schedule P

This schedule is not scientific and should be deleted. The Storage condition and the shelf life should be supported by stability studies and should be part of application for Marketing Authorization

Schedule P1

This schedule should be deleted. The pack sizes should be decided based on the regimen and stability studies and should be as per the application for Marketing Authorization.

Schedule U

Instead of listing out specific activities in schedule U, provision for recording start and end time of each critical activity related to manufacturing should be included in Schedule M. Instead of signature of competent staff, signature of the person performing the activity and verifying the activity should be included.

Instead of listing parameters to be included in the COA, it should be stated that test results as per the approved product specification should be included. Instead of signature of Approved analyst, signature of reviewer should be included. (Concept of approved analyst should be eliminated)

Schedule V

Test for toxicity should be removed. 

The schedule should include requirements for grant of marketing authorization / manufacturing license for generic products (subsequent new products, drugs approved prior to 4 years). All drug applications should be submitted in CTD format and include necessary data to demonstrate safety and efficacy of drugs, stability, suitability of analytical methods etc'

Conclusion:

Government of India is already working on improvement of the drug laws and has taken suggestions from various associations. It is high to revamp whole system instead of doing some incremental improvements.  Above suggestions will certainly help in modernization of Drug laws and enforcement resulting in improvement in quality standards of drugs available in India.