Draft Rules to substitute existing Schedule M to bring in GMP on par with international standards
In my opinion, the Drugs and Cosmetics Act is well-drafted and has been amended from time to time with major changes in 1982 and 2008. Rules have a number of amendments and Good Manufacturing Practices are upgraded by amending Schedule M and Medical Devices Rules 2017.
New Drugs and Clinical Trials Rules 2019 have been incorporated. Draft Rules will substitute existing Schedule M to bring in Good Manufacturing Practices (GMP) on par with international standards. Major industry stakeholders want many changes in the draft rules as it is apprehended that it will require huge investment leading to an increase in prices. Medium and small scale industry is likely to be affected most. It has become a fashion to criticise Acts enacted in the pre-independence era.
There is a need for a revised drug classification system
India has made big strides on the World Bank’s ease of doing business index and Prime Minister Narendra Modi’s vision of minimum government and maximum governance. It is commendable but there is an urgent requirement to remove/amend “obsolete” regulations that have outlived their utility and hamper governance by creating avoidable confusion. There are many sections in the Drugs & Cosmetics Act and Rules 1940 & 1945 which needs to be identified on priority. One of them is the current classification of medicines.
Current classification of medicines in India under the Drugs and Cosmetics Act into Schedule G, H, H1, X is outdated, evolved through patchwork over the years and needs to be thoroughly updated. The primary aim of the scheduling system is to ensure appropriate access to medicines while balancing public health and safety. There is a need for a revised drug classification system that is more comprehensive in coverage and eliminates the overlaps between classes and addresses implementation challenges in the diverse and fragmented ecosystem in India.
Accessibility, affordability and lack of transparency are the major challenges in the sector of sale of medicines. These barriers could be effectively overcome by adopting technology, specifically the internet, into the healthcare system. In addition, it provides tracking and traceability of medicines, abuse prevention, addressing consumption of drugs without prescription, tax loss and value-added services for consumer empowerment in healthcare. Moreover, it will foster entrepreneurship, innovation, attract foreign direct investment and create jobs. These are all key areas of national development.
The CDSCO should enforce all drug-related laws throughout the country
The following areas may be considered before redrafting the Drugs and Cosmetics Act and Rules.
- Enforcement of the act
Present scenario: Partly enforced by the Central Government and partly by State Governments.
Result: Uneven enforcement of the rules by the States. The industry grows in some encouraging States only. Clandestine activities in some States with the connivance of officers affect the entire nation.
Suggestion: The CDSCO should enforce all drug-related laws throughout the country.
- Manufacturing Licensing Policy
Present scenario: Loan licences, third party arrangements, manufacturing and marketing arrangements, lending of trade names etc., are being resorted to.
Result: Actual manufacturer suffers in the sales. Sub-standard, not of standard quality, cheap products, unhygienic preparations flood the market. The government is cheated of taxes by the tricks played by large manufacturers. Helps them in money laundering business and to amass black money.
Suggestions: All such unprincipled practices should be banned. Natural justice should be brought back.
- Cold Chain
Present scenario: Only some reputed firms maintain cold chains in distribution.
Suggestions: Even small scale manufacturers and loan licensees should follow it strictly.
- Competent Technical Staff
Present scenario: All science graduates are eligible to become CTS.
Results: Professional pharmacy graduates are unemployed. Quality cannot be built into drugs.
Suggestion: Only pharmacy graduates registered in the pharmacy council, should become CTS for manufacturing and testing. 18-months experience also should be waived. D.Pharm should be approved for quality control CTS as they are more technical than BScs.
Any change should be phased out over a span of a few years while harmonising ICH framework
While the industry is undergoing a paradigm shift towards quality-driven procedures, it is good to see that the national regulators have decided to reframe the guidance. The key focus for the revision should be on harmonisation of quality practices, GMP/GLP requirements, safety and efficacy that would directly benefit the patient population with high-quality medicines. Focusing on these key areas in the upcoming revisions should bridge the gap between the Indian Drugs and Cosmetics Act 1940 and global regulatory standards (ICH, WHO, US-FDA and other regulatory guidance). However, this shift in practice would have a significant implication on the cost dynamics of the product.
Any change should be phased out over a span of a few years, harmonising the ICH framework first and then going into detailed execution to meet the quality standards of other regulated markets. Pharma manufacturers in the Indian market, supplying product to India should be given time to implement quality into systems in a cost-efficient manner. If implemented overnight there will be significant disruptions. On the commercial side, the government should also consider having different price ranges, ceilings and floors for products depending on the therapeutic area of focus, availability and affordability.
Involve pharmacy academicians across the country in making a new law
The Drugs and Cosmetics Act 1940 is archaic and belongs to the British medieval period. In the present scenario, the Act has to deliver robust and safe regulation to meet present-day needs.
What we need is a strong regulatory framework for infrastructure, access to safe and effective medicines, closely monitored clinical trials, cut down on fixed-dose combinations of drugs and encourage single dosage forms. Due to the advent of newer drug delivery systems and dosage forms, the Act needs a complete relook to meet future regulatory needs of the country. It should be simple and easily implementable in a complex country like ours. This should also suit the future medical devices and drug delivery systems which will soon flood the market in the coming years.
Generic drugs should be encouraged in our country to meet the wider aspirations of our public healthcare system. Incorporate recent WHO norms to meet the needs of our country’s huge population. Make graduation in pharmacy compulsory to run pharmacies as done by our neighbours like Bangladesh and Sri Lanka. Involve pharmacy academicians across the country in making new law.
Future amendments of Drugs and Cosmetics Act should provide statutory powers to the CDSCO. The new law should also help in encouraging new drug discovery in the country. This will save a huge tranche of foreign exchange and ensure the availability of affordable drugs to our populations. It will also help fulfil our Prime Minister’s dream of creating an Atmanirbhar Bharat in manufacturing and dispensing of medicines.
The Act needs to be comprehensive, transparent and simplified
The Government of India through the Drugs and Cosmetics Act has made provisions regarding import, manufacturing, sale and distribution of drugs and cosmetics. Despite several subsequent amendments, the Act needs to be more comprehensive, transparent and simplified looking at the current scenario of the pharma market in India. Some of the key considerations are as below:
• Digital platform to be developed to track prices of drugs sold in the market to ascertain compliance to DPCO norms and submission of pricing made by Industry to increase transparency. This will help reduce price overcharging and litigations.
• Drug serialisation to be done for domestic sales to reduce the spurious drugs, counterfeiting and product diversion.
• Considering India as emerging export hub clear guidelines/approval mechanism to be defined by the Central/State FDA for resale of raw material not used by EOU. This will help bring efficiency and reduce material expiry at EOU.
• Information about the availability of medicine, prices, discounts and generic versions of the said medicine to be made available to all the consumers through a digital platform. For e.g., discounts offered by the manufacturer are not fully passed to consumers by retailers in a standardised form, drugs with the same molecular combinations are available in branded as well as generic forms at different prices.
• Clear jurisdiction/approval mechanism to be defined for drug approval between Central and State authorities
The D&C Act should have a Central Licensing System
The issue of refurbishing of the Drugs & Cosmetics Act 1940 is being discussed for a long time and it is necessary to make it at par with the global regulations without further delay. My suggestions to the lawmakers in this regard are:
- In line with the most developed countries, the D&C Act should have a Central Licensing System for all pharma products to avoid approval of irrational FDCs for human/animal consumption at the State level. Some of the FDCs may be considered for inclusion in IP based on their merits.
- If a medical device is already approved by the US FDA or EU Regulations, it should not be treated as a Drug and suitable amendments should be made in D&C Act 1940 in Section 3b (iv) accordingly.
- Since ‘Schedule M’ applies to all manufacturers of API and pharma products and specific requirements have been framed for various dosage forms and respective facilities, the system for giving separate manufacturing licenses for Schedule C and C1 drugs and other than Schedule C and C1 drugs should be abolished. The approved manufacturing section/s should be mentioned on the license and accordingly, the product approval may be granted, subject to other technical compliance with regard to safety, efficacy and quality.
- The manufacturing license should be granted for life unless suspended by the drug authorities or withdrawn by the manufacturer. However, it should be mandatory for the licensee to pay the renewal fees after a specific period. If the licensee does not pay the renewal fees in the given time it should get automatically cancelled.
- Similarly, a single license should be issued for the wholesale or retail sale of drugs and pharma products. A comprehensive list of drugs that need prescription of a medical practitioner and a list of drugs that do not need prescription of a medical practitioner should be prepared and the sale of OTC products should be regularised.
- Rule 96 and 97 should be suitably amended to have minimal labelling requirements, but effective against misuse and should be customer/patient-friendly. Product leaflets should be mandatory in the case of OTC products.
The expiry period to a pharma product, except Schedule P1 drugs and drug products, should be granted to the manufacturer at the time of approval of the product based on stability studies, impurity profiling and in-vitro bioequivalence data. Expiry date need not be necessarily based on the expiry date of the API.
The void in the D&C Act is the absence of guidelines for FDCs
In the last 15 years, a lot number of amendments have been made in the Drug and Cosmetics act including chapters on clinical trials, medical devices, Schedule M on GMP. The act now exists in a much-improved form, but for satisfactory implementation, a global reach is necessary by studying and analysing the provisions given and followed in the international acts of different countries.
In our country, the void that exists in the Drug and Cosmetics Act is the absence of guidelines for ‘Fixed-Dose Combinations’ in the act itself. Perhaps the FDA authorities should be aware that most of the existing FDCs in this country are actually perceived by the marketing departments of different companies, thus lacking a proper rationale pharmaceutically.
The Drugs and Cosmetic Act has to be amended with proper guidelines in this area to avoid any untoward adverse drug reactions and make the treatment more scientific and safer for the patients.
It is one thing to decentralise the Drug control authorities into state licensing points. It is yet another to have Central Government’s Control through CDSCO to give out amended guidelines for avoiding mishaps in the country in terms of irrational FDCs.
A certain amount of handholding is necessary to accomplish this task and for smoother passage of future FDCs in this country.
The Government needs to collate the list of NDDS and put it up at the earliest
As a nation of a billion-plus people, we need to focus on the efficacy of conventional dosage forms for the benefit of their healthcare needs. It is heartening that a key amendment was made to the Drugs & Cosmetics Act vide GSR 327(E), dated April 3, 2017, to ensure that a generic drug is as efficacious as the first product approved by the CDSCO (designated as Reference Product) therapeutically. The said notification, which is in line with the international regulatory landscape, makes it mandatory to establish ‘Bio-Equivalence’ of the generic drug, with the reference product already approved by the DCGI.
Recently CDSCO has listed “Reference Products” on its website, against which subsequent generics will be approved based on successful bio-equivalence studies.
Novel Drug Delivery Systems (NDDS) are gaining popularity the world over. NDDS are modified versions of conventional dosage forms. An NDDS formulation provides superior efficacy or safety or both, as compared to the conventional dosage form of the same drug. NDDS are developed using unique additives and/or advanced technology.
On March 19, 2019, CDSCO issued GSR 227(E), which includes NDDS in the Act. The said GSR recognises that all NDDS are New Drugs and shall always be deemed so. This means that the subsequent applicants of a CDSCO-approved NDDS will be required to establish safety as well as efficacy equivalent to the original Reference NDDS Drug by conducting pre-clinical and clinical studies with “Reference Product” as a comparator as per NDCT Rules, 2019.
In view of the above GSR, it is now imperative for CDSCO to identify and separately list out the NDDS products in the market and then decide the “Reference Product” of each approved NDDS.
CDSCO should subsequently disseminate the information by putting up the list on their website. If this is not done, approvals for NDDS may be issued by State Drugs Controllers (instead of CDSCO), without establishing ‘Therapeutic Equivalence’.
A list will also guide the subsequent applicants of the NDDS to choose the correct Reference NDDS Product, and thereafter establish ‘Therapeutic Equivalence’ of their NDDS with the Reference NDDS.
The Government needs to collate the list and put it up at the earliest on the CDSCO website.
Training of regulators and industry personnel must be emphasised
The D&C Act looks like a gamut of all the systems of medicines practised in India in a single volume. It needs to be in line with 21st-century global regulations. Considering the concept of new drugs in the Indian context (at present) and how does it differ from ANDA & NDA (in the global context), there is a need to make the regulations much simpler and uniform. Adequate referencing to ICH, WHO-GMP, ISO 9001-2015 and ISO 14000 guidelines must be ensured.
The domestic market in India, 2019-20 is 1.4 lakh crores and exports 1.22 lakh crores and medical devices Rs. 62,000 crores, this may double by 2030. The Drugs and Pharmaceuticals Act be relevant to today’s Indian and global drug development, availability to consumers of all economic background at a reasonable price.
I would like the new Drugs Act to be renamed as (Drugs and Pharmaceuticals Act 2020) for the drugs of chemical origin, biosimilars, biologicals and medical devices. It also must be aligned with global standards and regulatory requirements. It is really too expensive if the development and manufacturing have to be redone for new registrations.
We have pharmacopoeias for drugs of vegetable and herbal origin, veterinary products. Food is controlled by PFA and FSSAI.
Manufacture of cosmetics, Ayurvedic, Siddha and Unani drugs, Homeopathic medicines and Veterinary drugs are meant broadly for domestic consumption, hence the controls to ensure specification and quality standards the benchmark can be decided based on the best and abundant supply of materials. For exports, if the countries have specific guidelines that can be complied. There may be a need for specialised qualifications for the regulators.
I do not see the relevance of multiple standards for compliance for different markets except pharmacopoeia specification and compliance. Important controls for cGMP are vendors, air, water, cross-contamination, adhering to SOPs, online documentation and recording deviations. The training of regulators and industry personnel must also be emphasised. The approvals of manufacturing and analytical chemists should be more stringent.
The emphasis should be to create a proactive deterrent mechanism than a reactive, punishment-based regime
The Drugs and Cosmetics Act 1940, enacted during British Rule, is due for review and complete overhaul. India is now a net exporter of drugs, third-largest in the world in terms of volume. Nearly a hundred countries depend on India for the supply of essential medicines. More importantly, due to the federal nature of the country, we have both State and Central Authorities.
The Act should now reflect global stringent regulatory requirement and at the same time should be sensitive to the affordability of the medicines for the masses. The time has come to include good distribution practices (GDP), including supply chain logistics.
In the modern era, the emphasis should also be on environment-friendly practices in manufacture, supply and distribution of drugs as well as safe disposal of unused and expired medicines, wastages arising during manufacture.
This is especially important in the case of antibiotic residues to prevent the development of resistance. There is also an urgent need to make the rules dynamic in nature rather than static. The emphasis should be to create a proactive deterrent mechanism rather than a reactive, punishment-based regime. While carrying out a review of the Act, it would be prudent to hold wide-ranging consultations with all stakeholders.
Currently, there is dual control by State and Central regulators which sometimes does not promote ease of doing business and there is duplication of work and authority. This situation is not in line with practices recommended by international groups like PIC/s. If the country wants to join these international groups, we might have to think about establishing a single authority and possibly separate drug administrative services, similar to civil services like IAS.
There is also a need to create a conducive atmosphere to promote high-end research in the country, in partnership with academia. The Act needs to incorporate aspirations of the academia and legal recognition of their work. In case, India has to climb up the value chain, the role of the academia will be very crucial.
Overall, the Act should reflect the aspirations of the profession which has the potential to provide large scale, knowledge-based employment as well as provide quality and affordable medicines to the masses of the world.
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