Manufacture / manufacturer regulatory controls

Contracting out of activities previously only conducted in-house is already becoming quite common and will probably continue to develop. In the past a so-called full-service pharmaceutical company took direct responsibility for all the activities required for the formulation, manufacture, quality control, and regulatory approval of its drug products. Nowadays the use of specialist contract houses to perform activities such as formulation, analytical methods development, manufacture of clinical trials supplies, supervision of the assembly of an NDA, postmarketing surveillance, and even troubleshooting may be contracted for even by some of the largest companies. 

Regulatory authorities such as the FDA have prepared guidelines on comparability protocol, Comparability Protocols—Chemistry, Manufacturing and Controls Information, to enable manufacturers to follow a plan to establish and substantiate that changes to postapproval processes do not affect drug quality. 

In some cases, drug materials are isolated from natural products. In other cases, natural product extraction constitutes the raw material or intermediate for production of the drug via a semisynthetic route. Methods for chemical reactions, product purification, control parameters, and analytical procedures are developed and they form the basis for the chemistry, manufacturing, and control (CMC) information for regulatory application. 

The methods employed in the manufacture of biological medicinal products are a critical factor in shaping the appropriate regulatory control. Biological medicinal products can be defined therefore largely by reference to their method of manufacture. Biological medicinal products prepared by the following methods of manufacture will fall under the scope of this annex ... 

This book is intended for formulation scientists, analytical scientists and engineers, regulatory and compendia personnel, procurement personnel, preclinical scientists, excipient manufacturers, quality control and assurance personnel, and distributors. 

A second category comes under the heading, illicit, when the dosage form is manufactured without any regard for regulatory control. Such products can come under two general types ... 

Sophia Y.L. Paspal, PhD Global Regulatory Affairs-Ghemistry, Manufacturing, and Control W/eth Research Collegeville, Pennsylvania... 

In some installations, alternative approaches for regulatory control may be required. Where a variety of products are manufactured, the reactor may be equipped with alternative heat removal capabilities,... 

Then, preferably at an off-site location (to avoid any interruptions) the panel should meet with the corporate regulatory NDA team [presumably Regulatory Director, Medical Director, Chemistry, Manufacturing, and Control (CMC) Director, and others as appropriate] with a detailed grilling and discussion. The idea is to dissect the entire document and to closely question the corporate team on all aspects. 

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