Regulation of Quality Standards of Pharmaceuticals

Drugs are not just ordinary consumer products hence if they are not with certain quality, efficacy and safety can be dangerous. Therefore it is the responsibility of national regulatory authorities to protect the patient from harm. (Lembit Rago, 2014)

Pharmaceutical industries are considered as the highly regulated industries. For execution of the rules and regulations and issue the guidelines to regulate drug development process, licensing, registration, manufacturing, marketing and labeling of pharmaceutical products and many other things a regulatory body is present in every country, like USFDA(USA), MHRA(UK), CDSCO(India), HEALTH CANADA(CANADA), MCC(South Africa), ANVISA (Brazil), EMEA (European Union), SFDA (China). Along with these there are some of the international regulatory agencies and organizations such as World Health Organization (WHO), Pan American Health Organization (PAHO), World Trade Organization (WTO), International Conference on Harmonization (ICH), World Intellectual Property Organization (WIPO) which play essential role in all aspects of pharmaceutical regulations related to drug product registration, manufacturing, distribution, price control, marketing, research and development, and intellectual property protection. These bodies work to ensure the safety, efficacy, and quality of drugs available to the public. The major challenges of these regulatory bodies are: protect the public from harmful and suspicious drugs, the establishment of proper legalization covering all products with a medicinal claim and all relevant pharmaceutical activities, whether carried out by the public or the private sector, to increase worldwide regulatory growth to ensure the safety of people. (Geetanjali Sengar*)

Major drug and pharmaceuticals regulating bodies in India involve:

• Central Drug Standards and Control Organization (CDSCO)- This comes under the guidance of the Ministry of Health and Family Welfare. CDSCO recommends standards and measures for ensuring the safety, efficacy, and quality of drugs, cosmetics, diagnostics and devices in the country, regulates the market approval of new drugs and clinical trials standards. It also controls drug imports and approves licenses to manufacture the products that are mentioned above.
• National Pharmaceutical Pricing Authority (NPPA)- Instituted in 1997 under the Department of Chemicals and Petrochemicals. It fixes or revises the prices of bulk drugs and formulations at judicious intervals; periodically updates the list under price control through inclusion and exclusion of drugs according to guidelines.
• Drugs Controller General of India (DCGI): It governs the things with respect to licensing and quality control issues, market authorization is regulated by the Central Drug Controller, State drug controllers have the authority to issue licenses for the manufacture of approved drugs and monitor quality control, along with the CDSCO.

A system involving dual regulatory control which exists at both Central and State government levels. The central regulatory authority carries out approval of new drugs, clinical trials, standards setting, control over imported drugs and coordination of state bodies’ activities whereas state authorities undertake responsibility for issuing licenses and monitoring manufacture, distribution and sale of drugs and other related products.

A huge issue relating to the different quality of drugs exists in our Indian market. The drugs which are exported are of higher quality, to meet the required standards in the country of export, whereas the drugs in the local market are of local quality standards which are fixed by the regulating body. Also because of the deficiency of transparency in licensing procedures has resulted in the market being flooded with counterfeit and substandard drugs. As per the Mashelkar Committee report, nearly 30% of the Indian market was flooded with spurious, substandard or counterfeit drugs.

To match with the global quality standards, proper regulation is necessary on the quality of the drugs that are manufactured in our country. Hence some modifications are done in the schedule M (which describes regulations related to GMP) which will help to enhance the quality of the drugs. Schedule M is revised which advises proper pressure differentials in the areas of operation. A dedicated air handling units with an adequate number of air changes can be used to achieve these pressure differentials. This will help to eliminate or reduce the chances of cross-contamination between the products. Also, the emphasis on cleaning validation of the equipment and the processing areas is given in revised schedule M whenever there is product change over. Current status should be displayed on equipment to avoid mix-up or contamination, stability study should be conducted to determine the re-test period and expiry date, etc. (Dr. J Ramniwas, 2012)

The aim of GMPs is to minimize risks with regard to the manufacturing, packaging, testing, labeling, distributing and importing of drugs, cosmetics, medical devices, blood and blood products, food items etc. These protocols are largely concerned with parameters such as drug quality, safety, efficacy, and potency. WHO also gives guidelines relating to the GMP to ensure consistency in quality, safety and efficacy standards while importing and exporting drugs and related products in different countries. In India, the WHO-GMP certification is given having a validity of two years, that may be granted both by CDSCO and state regulatory authorities after a thorough inspection of the manufacturing premises.

The requirements specified under the upgraded Schedule ‘M’ for GMP have become mandatory for pharmaceutical units in India. According to the study, units in states like Gujarat, Karnataka, Maharashtra and Andhra Pradesh have achieved a high percentage of Schedule M compliance in comparison to units in other states.

Apart from drugs, special guidelines are given for the manufacturing of medical devices. After the case involving unapproved and untested stents on 60 patients in JJ Hospital, and the subsequent recommendations made by the Mashelkar Committee in 2004, the DCGI formulated a new set of guidelines for the import and manufacture of medical devices in the country in June 2007. The Committee recommended creating a specific medical devices division within the CDSCO in order to address the management, approval, certification and quality assurance of all medical devices. Quality regulation of biological products is also important. The rules for the manufacture, use, import, export and storage of hazardous microorganisms or genetically engineered organisms or cells are given under The Ministry of Environment and Forests under the Environment (Protection) Act of 1986. As per these rules, biological materials are regulated from the R&D stage to their release in the environment.

Committees which regulate this includes The Institutional Biosafety Committee (IBSC), Review Committee on Genetic Manipulation (RCGM) and the Genetic Engineering Approval Committee (GEAC). In addition, the DCGI and state drug controllers as per the Drugs and Cosmetics Act 1945 and its subsequent amendments regulate biologicals.
The current regulatory system still facing some challenges like:

Currently Indian market is highly occupied by spurious and substandard drugs, Uniform implementation of regulatory procedures may be affected by dual licensing mechanism, Lack of transparency in licensing procedures, Difficulty in implementing uniform standards because of insufficient regulatory expertise and testing facilities, There is a need of coordination, accountability and transparency in functioning among different ministries concerned with drug regulation in India.

Recent Regulatory Initiatives

Establishment of National Drug Authority which is an integrated system that regulates quality as well as a price control. Also, many pharmacovigilance centers at national, zonal and regional levels are established which monitors adverse drug reactions, Monitoring of clinical trials is more strengthened by setting up of the Clinical Trials Registry of India (CTRI) (5. REGULATORY ISSUES IN THE INDIAN PHARMACEUTICAL, n.d.)

Clinical trials are the key tools in new drug evaluation. Institutions like DCGI, DBT (department of biotechnology), ICMR (Indian council of medical research, CBN (central bureau of narcotics), RCGM (review committee on genetic manipulation) GEAC (genetic engineering approval committee) play a prominent role in guiding the clinical trial in India. Currently, regulations related to clinical trials are given in the Schedule Y of the drug & cosmetics rules, 1945.

To bring the Indian regulations up to balance with internationally accepted definitions and procedures schedule Y is extensively revised after the amendment of the D&C actin 2005. The changes which took place were

• Definitions for Phase I-IV trials, which eliminated the Phase Lag
• Clear responsibilities for investigators; and sponsors.
• Requirements for notifying changes in the protocol (Ramu B, 2015)

USFDA has introduced a new concept – Quality by design which is a new perspective on product development. This aim to understand the design and development of the pharmaceutical formulations and manufacturing processes to help ensure the quality of the end product. Submission of Quality by Design (QbD) document is made mandatory by USFDA for all the New Drug Application (NDA) applicants from January 2013. Hence International Pharmaceutical Excipients Council (IPEC) has urged all the Indian manufacturers exporting to the US to apply this concept. (Dr. J Ramniwas, 2012)

Hence to comply with the international quality standards regulatory agencies need to fulfill some loopholes, as well as agencies, has to introduce some new regulations.