Quality Systems

Forty years ago, investors and business speculators shuddered at the prospect of working with India's pharmaceutical industry. The industry was plagued by archaic patent laws and insufficient infrastructure, and only multinational companies (MNCs) were able to exploit its crude resources and monopolistic legal framework. Struggling in the shadows of these MNCs were the Indian pharmaceutical entrepreneurs and a handful of producers. Because more than 70% of the pharmaceutical market value was in the hands of MNCs, India's indigenous pharmaceutical industry was floundering. Its amount of exports was negligible, and the domestic market outlook was bleak because of onerous government regulation.

BIO Raises Concerns About Studies on Follow-On Biologics; Green Chemistry Reduces Costs and Waste; Novel Polymer–DNA Delivery System; WHO Stresses Lack of Capacity for Pandemic Flu Vaccine; EGA Concerned About Regulatory Workload in Approving Generics

The enactment of the Indian Patents Act of 1970, implemented in 1972, provided an open platform to the Indian pharmaceutical industry to adopt process patents to manufacture active pharmaceutical ingredients (APIs) and formulations without fear of infringement of product patents. This resulted in a phenomenal growth in the number of pharmaceutical manufacturing units, from 2257 in 1970, to 5156 in 1980, 16,000 in 1990, and more than 23,000 in 2005. This was accompanied by a steep increase in investment from Rs. 2.25 billion (approx. $250 million US) in 1973, to Rs. 45 billion (approx. $1 billion US) in 2002–03. The prices of the most advanced drugs dropped significantly in India, leading the Indian pharma sector to become more competitive while remaining extremely cost effective in the global market.

The concept of Acceptable Analytical Practices (AAPs) was developed by the Analytical Technical Group of the Pharmaceutical Research and Manufacturers of America to share information about how the pharmaceutical industry has implemented chemistry, manufacturing, and controls and quality guidances of the International Conference on Harmonization and worldwide regulatory authorities. The AAP process identifies and addresses critical issues in which guidance is lacking, ambiguous, or contradictory. AAPs were designed to provide a forum where one could learn from the experience of experts in pharmaceutical analysis and enhance the understanding of analytical practices that reflect good science and sound regulatory compliance. This article summarizes the discussion points from a meeting regarding the Justification of Specifications topic.

Mishaps in packaging labels serve as a reminder: the recall is in the details.

FDA is buried in postapproval manufacturing submissions and seeks to reduce the scope of changes that require agency scrutiny.

This article considers the distinction among the terms qualification, validation, and verification in the context of pharmacopeial usage.A recommendation for a standardized usage of the terms validation and verification is provided,and general requirements for validation and verification activities are given.The article also emphasizes the importance of knowing when validation or verification is necessary relative to the use of a method to satisfy pharmacopeial article requirements (for which a monograph exists in the pharmacopeia) or for nonpharmacopeial use.

Indian pharmaceutical machine manufacturers (IPMMs) are exceptional among their foreign counterparts. Historically similar to the Chinese with regard to copycat practices, patent infringements, and substandard quality, the IPMMs have made great strides in innovation and collaboration to break free from the shackles of this paradigm.

Missed or late calibration dates can accumulate, and even if the equipment is labelled appropriately, it can suggest poor management of resources and priorities.

Rockville, MD (Mar. 1)-Sending Warning Letters to 8 manufacturers and 12 distributors, The US Food and Drug Administration ordered a stop to the manufacture and distribution of unapproved drug products containing ergotamine tartrate.

Just because the wheels are turning doesn't mean they're going forward.

The proposed rule would impose new record-keeping requirements on some 1200 manufacturing establishments.

The authors describe the methods by which precise analyses of stable-isotopic abundances can be used in security and forensic applications for pharmaceutical materials. These methods include product and process authentication of raw materials, pharmaceutical intermediates, drug substances, formulated drug products, and synthetic pathways. Collectively, these methods can be used to investigate and mitigate patent infringement. In the future, more complete examples will be presented containing full isotopic results and the application of the methods described in this article.

FDA's new safety program, Critical Path Initiative, and user-fee proposal seek to reinvigorate pharmaceutical R&D.

Washington, DC (Feb. 22)-The Biotechnology Industry Organization criticized two separate studies respectively released by the Pharmaceutical Care Management Association and Express Scripts, Inc. regarding the cost-savings, interchangeability, and market penetration of follow-on biologics.

Brussels (Feb. 13)-The European Generic Medicines Association raised concerns over what it terms ?the serious lack? of resources available to member states in the European Union (EU) to deal with the regulatory workload and bottleneck in new registrations caused by the new Decentralized Procedure (DCP) for approving drugs in Europe.

Rockville, MD (Jan. 5)-The US Food and Drug Administration issued a Warning Letter to Bell-More Laboratories following the agency?s August 2006 inspection of the company?s Hampstead pharmaceutical facility.

Rockville, MD (Feb. 1)-The US Food and Drug Administration issued a revised warning letter to Actavis Totowa, LLC, citing ?significant deviations from the current Good Manufacturing Practice regulations.?

Princeton, NJ (Feb. 15, 2007)-Ranbaxy Inc., confirmed that federal officials conducted a search of its New Jersey offices on Feb. 14, 2007 and commented on its reported plan to acquire Merck's generics business.

InformexUSA, San Francisco (Feb. 14)-The Synthetic Organic Chemical Manufacturers Association is launching a new sustainable chemistry initiative, the International Center for Sustainable Chemistry.

Washington, DC (Feb. 7)-The Synthetic Organic Chemical Manufacturers Association (SOCMA) submitted comments to the US Department of Homeland Security in response to proposed DHS regulations on chemical site security, asking DHS to take into consideration the unique nature of the specialty batch manufacturing sector.

The injunction blocks rules that required secondary wholesalers to supply pedigrees tracing the chain of custody to the maker.

As technology for impurity analysis improves, scientists are gaining better information and asking for more regulatory guidance.

"Quality by design" (QbD) and "quality risk management" at long last seem to be moving from the buzzword stage to becoming important influences on drug development and manufacturing. A series of quality standards issued by the International Conference on Harmonization (ICH) is encouraging the adoption of common quality-based drug manufacturing approaches designed to reach the "desired state" of drug manufacturing (i.e., more efficient, agile, flexible operations that can reliably produce high-quality drug products with less regulatory oversight). These developments reflect increased pressure to make pharmaceutical manufacturing more efficient and less wasteful and to encourage regulators in all regions to focus on the most critical issues affecting product quality and patient safety.

It's what's on the outside that counts, too.