ARCHIVED - Drug Establishments: Reviewing the Good Manufacturing Practices Inspection Program

Consultation Workbook Introduction

Welcome

Health Canada is reviewing its Good Manufacturing Practices (GMP) inspection program. Our goal is to make our inspections of drug establishments more risk-based. The review involves a detailed evaluation of all aspects of the GMP program, including such things as inspection scheduling and the conduct of inspections. Several factors highlighted the need for a review at this time, including the growing complexity of health products now available on the Canadian market and international trends related to GMP inspections.

We are exploring several changes and we would appreciate your input, as an industry stakeholder, on key concepts that we are considering.  Specifically, we welcome your input on (i) how we assess the risk of an establishment; (ii) appropriate inspection cycles for different levels of risk; and (iii) tools that can be developed to make the inspection program more risk focused.

The following suggestions may help you prepare your comments:

• Please explain your views as clearly and concisely as possible.
• Be sure to distinguish between what you support and what you object to in  this document.
• Provide the rationale for your views, particularly your concerns, with facts,   data or specific examples.
• Describe any assumptions that you made.
• Please submit your comments by the deadline of November 30, 2009.

Please note that any information collected will only be used for input to this consultation. The information collected will be used to create a summary report and will guide recommendations made as part of the GMP Review. The summary report will be made available to stakeholders once consultations are complete.

About You

Appendix A

Glossary

Compliance

state of conformity of a regulated party (including a corporation, product with an institution, individual or other legal entity) to a legislative or regulatory requirement

Compliance Monitoring

actions planned to maintain regular surveillance in order to evaluate compliance with applicable requirements of the Food and Drugs Act (FDA) and its associated Regulations; includes a wide variety of fact gathering and assessment activities such as inspections, market surveys and a product sampling program

Drug

any substance or mixture of substances manufactured, sold or represented for use in:

1. the diagnosis, treatment, mitigation or prevention of a disease, disorder or abnormal physical state, or its symptoms, in human beings or animal;
2. restoring, correcting or modifying organic functions in human beings or animals;
   or
3. disinfection in premises in which food is manufactured, prepared or kept

Inspection

on-site monitoring and assessment against the applicable requirements of the FDA and its associated Regulations; inspections are routinely conducted on a pre-determined cycle or as required to assess compliance

Inspector

any person designated as an inspector for the purpose of the enforcement of the FDA under subsection 22(1)

Risk

the combination of the probability of occurrence of harm and the severity of that harm

Risk criteria

the factors considered in determining an establishment's risk level or rating

Risk assessment

a systematic process for organizing information to support a risk decision; for purposes of inspection scheduling culminates in determination of inspection frequency

Appendix B

The United Kingdom's Medicines and Healthcare Products Regulatory Agency (MHRA)

The MHRA identifies a site's relative risk to determine appropriate inspection frequency:

1. Prior to an inspection, a company is required to file a compliance report, which includes a list of the changes since the last inspection and a signed statement from the senior manager, who is accountable for performance, which serves as evidence of conformance to the requirements.
2. The inspector reviews the compliance report, and the last inspection report, in preparation for the inspection.
3. After the inspection, the inspector assigns a provisional risk rating based on the number and classification of observations.
4. The inspector then looks at other risk factors that may affect the risk rating:
   • significant concern over robustness of quality system
   • significant failures to complete actions to close previous deficiencies
   • significant nature of future changes on site
   • complexity of site
   • site  recalls since last inspection
   • site  rapid alerts since last inspection
   • concern over batch specific variations submitted since the last inspection
   • regulatory action related to the site
   • other (for example, did establishment report all changes in Compliance Report)
5. The inspector then assigns a final risk rating, which determines the general date of  the next inspection.
6. Finally, the inspection report, with risk rating and commentary, is sent to the establishment.

The United States Food and Drug Administration (FDA)

The FDA's risk-based approach to inspection scheduling considers risk factors related to facility, product and process. The facility's size, type, products and date of last inspection are weighted numerically and combined to produce a site risk potential (SRP).

Under the model, the SRP determines how soon a site will be inspected, and a site's chance of being selected for inspection increases if it

• has not been inspected recently
• has a higher production volume
• has a history of significant violations
• makes products associated with a high frequency of recalls and/or serious defects, uses processes expected to have a greater potential for cross-contamination and/or loss of a state of control
• makes sterile and/or prescription drugs

SRPs are then used to organize companies into tiers:

An annual list of firms requiring priority inspection is compiled and district offices determine the depth of coverage of each inspection.