Excipient Auditing

Is the manufacturer of the active substance and critical excipients audited and certified and well known or is little known about that company ... 

It is also a guideline to ensure product quahty through the suitabihty of the manufacturing equipment, air and water quahty, sanitation, insect and rodent control, and housekeeping. The FDA periodically sends inspectors to audit chemical companies who manufacture bulk pharmaceutical chemicals or inactive ingredients called excipients to ensure conformance. Whereas GMP conformance ensures that the product meets pharmaceutical quahty standards, it does not ensure conformance to customer-service-related requirements. 

For any new excipients, APIs or drug products (where new does not necessarily mean novel, but new to the receiving site) there are additional testing criteria, e.g. supplier audits, third-party contract laboratory audits, analytical method transfers, sample management/tracking, etc. For those key excipients, where there is on-site historical experience, it still behoves both parties to check whether the local grade/supplier used by the CMO is equivalent to that used by the supplier (Worsham, 2010). There are many examples of differences in excipient physical properties, e.g. particle size, which have been attributed to different excipient sources that could ultimately impact on the performance of those excipients in formulated products (Frattini and Simioni, 1984 Dansereau and Peck, 1987 Phadke et al., 1994 Lin and Peck, 1994). 

This chapter is meant as a survey of the manufacturing issues in the production of pharmaceutical excipients. As such many important decision points have been discussed. It is a basic tenet of GMP compliance and a principle of auditing that... 

The manufacturer and user should mutually agree upon the excipient specifications. The manufacturer must have the facility and process capability to consistently meet the mutually agreed upon specifications of the excipient(s). Subcontracting or significant changes to a supplier s audited process that could affect the physical, chemical, or functionality of the excipient in a final dosage form should be immediately communicated or pre-approved as mutually agreed upon between customer and supplier. 

The purchaser should verify that the supplier of raw materials, components, and services for the manufacture of excipients has the capability to consistently meet the agreed-upon requirements. This may include periodic audits of the vendor s plant, if deemed necessary. Purchasing agreements should contain data clearly describing the product ordered, including where applicable, the following ... 

Goode, S. A. IPEC GMP audit guideline for BPCs. Pharm Tech (Aug. 1999). Handbook of Pharm. Excipients. 3rd ed. APhA London Pharmaceutical Press (2000). Hirschom, J. O., Flanigan, T. Global GMP regulations for BPC facilities. J cGMP Comp 4(4), (July 2000). 

International Pharmaceuticals Excipients Council. Good Manufacturing Practices Audit Guideline for Bulk Pharmaceutical Excipients. (1997). 

Excipients can be crucial determinants of product performance and quality. Thus, they should be sourced directly from a reputable vendor who has quality systems in place to ensure consistent manufacture and control. Procurement from brokers is to be discouraged. Auditing such providers for the presence of quality systems and controls should be the norm, particularly if they are new suppliers to the pharmaceutical industry. A validation program should be put in place to establish reliability of the supply source. This program should take the following into account ... 

Good Manufacturing Practices (GMP) Audit Guideline for Distributors of Bulk Pharmaceutical Excipients. 

If the excipient or packaging material has been used previously in marketed products by your own pharmaceutical company, and the supplier has been audited, most of the information about these materials should already be available within the company. More often than... 

Section 5, General Auditing Considerations, sets forth key criteria to guide the audit of an excipient manufacturing facility. 

There should be a quality unit independent of production that has the responsibility and authority to approve or reject all components, in-process materials, packaging materials, and finished excipients. The quality unit should have the authority to review production records to assure that no errors have occurred or, if errors have occurred, that they have been fully investigated. The quality unit should be responsible for approving or rejecting excipients manufactured, processed, packaged, or held under contract by another company. The quality unit can delegate these responsibilities if proper controls such as periodic audits and documentation of training are in place. 

The excipient manufacturer should carry out a comprehensive system of planned and documented internal quality audits to verify whether quality activities comply with planned arrangements and to determine the effectiveness of the quality system. Audits should be scheduled on the basis of the status and importance of the activity. The audits and follow-up actions should be carried out in accordance with documented procedures. 

Inspection of an excipient operation may depend on the purpose of the audit and intended use of the excipient Operational limitations and validation of the significant processing steps of a production process should be examined to determine that the manufacturer adequately controls steps to assure that the process performs consistently. Overall, an inspection should determine the excipient manufacturer s capability to deliver a product that consistently meets the specifications listed in the marketed application, or the product specifications needed for research purposes. A team... 

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