Risk Classification of Observations made during Inspections of Blood Establishments (GUI-0061)

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Cover Letter

Our Mandate:

To promote good nutrition and informed use of drugs, food, medical devices and natural health products, and to maximize the safety and efficacy of drugs, food, natural health products, medical devices, biologics and related biotechnology products in the Canadian marketplace and health system.

Supersedes: October 31, 2005 (Draft distributed for comments)

Date issued: April 29, 2010

Date of implementation: April 29, 2010

Disclaimer

This document does not constitute part of the Food and Drugs Act (Act) or its associated Regulations and in the event of any inconsistency or conflict between that Act or Regulations and this document, the Act or the Regulations take precedence. This document is an administrative document that is intended to facilitate compliance by the regulated party with the Act, the Regulations and the applicable administrative policies. This document is not intended to provide legal advice regarding the interpretation of the Act or Regulations. If a regulated party has questions about their legal obligations or responsibilities under the Act or Regulations, they should seek the advice of legal counsel.

Table of contents

• 1.0 Purpose
• 2.0 Background
• 3.0 Scope
• 4.0 Definitions
• 5.0 Guide
  • 5.1 Assignment of the risk to an observation
  • 5.2 Responses to non-compliance
• References
• Appendix 1
  • Risk 1, Risk 2 and Risk 3 Observations

1.0 Purpose

To classify the observations noted during blood establishment inspections according to their risk.

To promote uniformity in the assignment of the rating following blood establishment inspections among inspectors of the Health Products and Food Branch Inspectorate (Inspectorate).

2.0 Background

Whole blood and blood components have been regulated as drugs under the Food and Drugs Act and Regulations since 1989 and Regulations for source plasma have been in place since 1979. During a blood establishment inspection, inspectors assess compliance of blood establishments that collect blood and blood components for transfusion purposes and plasma for further manufacturing against Part C, Division 2 and 4 of the Food and Drugs Regulations. The Annex to the GMP Guidelines, entitled "Good Manufacturing Practices for Schedule D Drugs, Part 2, Human Blood and Blood Components" provides specific guidance to the inspectors and stakeholders for the application of good manufacturing practices (GMP) to blood establishments.

It is important to note that this guide corresponds to the current regulatory framework. A new regulatory framework is being developed for blood and blood components and once in place, this guide will be revised accordingly.

The inspectors note all deviations and these are recorded as observations in the inspection Exit Notice. Situations of non-conformity must be well defined, unambiguous and directly supported by the applicable regulations. This guidance document will be used to assist inspectors to objectively and uniformly assign a risk rating to each observation noted.

An establishment will be rated overall compliant (C) if, at the time of the inspection, the regulated party has demonstrated that the activities it conducts are in compliance with the Food and Drugs Act and its associated Regulations as determined on the basis of the observation(s) made. A C rating does not mean that there are no observations or corrective actions required. An establishment will be rated non-compliant (NC) if, at the time of the inspection, the regulated party has not demonstrated that the activities it conducts are in compliance with the Food and Drugs Act and its associated Regulations. If the deficiencies compromise the safety of the product and/or pose an immediate or potential health risk to the donor or recipient, the establishment must immediately implement actions to minimize the risk of the implicated products. For example, the establishment may recall and/or place the implicated products under quarantine until the investigation is complete. POL-0001, Compliance and Enforcement Policy, will be followed when a non-compliance issue is identified.

3.0 Scope

This guidance document covers blood and blood components, to which Part C Division 2 of the Food and Drug Regulations applies, and is based on the current edition of the GMP. The guidance document also covers source plasma as it relates to Part C, Divisions 2 and 4 of the Food and Drug Regulations.

The Appendix attached to this document provides examples of situations or observations related to each category of risk. Please note that the list of situations or observations in the appendix is not exhaustive and that additional situations or observations may be added where appropriate.

The numbering system assigned to each section in the Appendix is a reference to the applicable regulations of Part C, Division 2 or Division 4 of the Food and Drug Regulations.

4.0 Definitions

The following definitions are provided to complement those already available under the glossary of terms in the current edition of the GMP Guidelines or other related documents referenced in the GMP Guidelines.

Observation: A deviation or deficiency to the Food and Drugs Act or Part C, Divisions 2 or 4 of the Food and Drugs Regulations noted during the inspection of a blood establishment and that is documented in the Exit Notice. The observations are classified as "Risk 1", "Risk 2" or "Risk 3".

Risk 1 observation:

An observation which describes a situation that has resulted or has a high probability of resulting in, an immediate or latent health risk to either the donor or the recipient of blood or blood components and may include any observation that involves fraud, misrepresentation or falsification of products or records.

Risk 2 observation:

An observation which describes a situation that has a low probability of resulting in an immediate or latent health risk to either the donor or the recipient of blood or blood components.

Risk 3 observation:

An observation that is neither Risk 1 nor Risk 2 but is a deviation from the Food and Drugs Act or Regulations.

Note 1: Although specific examples given in the Appendix are rated as Risk 1, 2, 3, a similar or the same observation could belong to a different risk category depending on the context, the specific situation, and the evaluation of the inspector.

5.0 Guide

5.1 Assignment of the risk to an observation

While it is recognized that it is impossible to encompass every situation that may generate a risk, the risk assigned will be in relation to the impact on the safety and the quality of the blood or blood components.

The overall inspection rating assigned is based on the risk involved taking into account the nature and extent of the deviations from the relevant Food and Drug Regulations.

Risk 1 observations, represent the highest level of risk and may have different impacts on the safety of the blood supply. The assignment of a Risk 1 observation may be given to a situation that affects components from a single donation or a situation that impacts a wider range of donations.

If one or more risk 1 observation (s) is noted during an inspection:

• The situation is immediately brought to the attention of the appropriate establishment's officials.
• The affected blood components are immediately put under quarantine and /or recalled as appropriate.
• The establishment must take corrective actions in order to prevent the situation from reoccurring.
• The situation may result in an "NC" rating.

For all categories of risk (1, 2 and 3), it is expected that all observations will be corrected within a timeframe appropriate to the level of risk and corrective actions required.

5.2 Responses to non-compliance

Compliance is normally achieved following a cooperative approach between the regulated party and the Inspectorate; however, when this is not possible, or when the regulated party is unable to correct non-compliance in a timely manner in order to ensure product safety, a number of regulatory measures may be used in accordance with POL-0001, to induce, encourage or compel compliance.

If the management of the blood establishment wishes to dispute the results of the inspection report, the "Dispute resolution and appeals" mechanism described in POL-0004, Good Manufacturing Practices (GMP) and Establishment Licensing Enforcement Directive, should be followed.

References

1.  Food and Drugs Act
2.  Food and Drug Regulations
3. POL-0001 Compliance and Enforcement Policy
4. POL-0004 Good Manufacturing Practices (GMP) and Establishment Licensing Enforcement Directive

Appendix 1

Risk 1, Risk 2 and Risk 3 Observations

Premises C.02.004

Risk 1 Observations

• No quarantine system in place for transmissible diseases reactive units
• No security for high risk areas - unauthorized personnel have access to areas such as laboratories and storage of blood and blood components

Risk 2 Observations

• No privacy given to the donor while completing the Record of Donation (RD) at the clinic
• No environmental control where required

Risk 3 Observations

• Site evaluation inspections (permanent and mobile) were not conducted at the required frequency
• No temperature mapping performed as required in storage area
• No certificate of calibration for temperature and monitoring device

Equipment C.02.005

Risk 1 Observations

• Critical equipment not maintained or calibrated to its specifications
• Critical equipment used in spite of evidence of a malfunction
• Testing equipment or computerized blood system employed without validation

Risk 2 Observations

• There is no documented evidence that the calibration protocol was followed
• Equipment does not operate within its specifications
• No equipment usage logs

Risk 3 Observations

• There was no documentation to show that maintenance was being performed in accordance with the manufacturer's specifications
• Preventative maintenance was not performed as scheduled

Personnel C.02.006

Risk 1 Observations

• Individual in charge of Quality Control (QC) / Quality Assurance (QA) does not hold a university degree or equivalent in a science related to the work being conducted and does not have sufficient practical experience in their responsibility area.

Risk 2 Observations

• No supervisory staff in the laboratory for transmissible disease testing or component production
• Delegation of QA responsibilities to unqualified persons

Risk 3 Observations

• There was no competency testing program in place
• Training Forms were not updated to reflect changes to SOPs and/or training matrix
• Version number of procedures not indicated in training records

Raw Material Testing C.02.009

Risk 1 Observations

• During review of RDs, it was noted that the donor answered yes to the question "In the past 6 months, have you had sex with someone whose sexual background you don't know?", yet the donor was not deferred.
• A deferral code for a sexually transmitted disease was not applied
• The deferral time frame assigned was shorter than required
• Aseptic techniques have not been followed during phlebotomy

Risk 2 Observations

• Incomplete documentation of acceptance criteria on the RD when product was released to inventory
• The donor completed the questions on the RD, including the ones that should have been asked by the nurse. However, the nurse did not verbally administer the applicable questions to confirm the donor's responses
• There was no double-blind verification for deferral codes manually entered into the computer system
• Confidential Unit Exclusion instruction sheet not clearly explained to donors
• No haematocrit or haemoglobin value recorded on the RD, as required
• The RD indicated that donor had visited a country, outside of Canada and the US, in the last 3 years, however, the specifics (i.e. city, town, village...) were not reported and therefore, malaria risk was not assessed
• The RD indicated that the donor had visited a malaria endemic area but no follow-up was conducted to determine time or length of visit
• There was no result recorded for presence or absence of skin lesions on the RD

Raw Material Testing C.02.010

Risk 2 Observations

• Vendors of critical supplies not audited as per the operating procedures

Manufacturing Control C.02.011

Risk 1 Observations

• Laboratory operating procedures were contrary to the manufacturer's instructions
• Staff did not follow operating procedures resulting in release of untested or quarantined products

Risk 2 Observations

• Components requiring irradiation were labelled as irradiated products prior to performing the irradiation
• Platelets were not equilibrated prior to agitation
• Deviations from instructions during production not documented and not approved by QA

Risk 3 Observations

• The bedside review of the RDs to be done prior to venipunctures, was not specified in a written procedure
• Unused labels were not destroyed according to the work instructions
• The documentation for Product Complaints and Adverse Transfusion Reactions were not in accordance with the requirements stated in the procedures
• There was no evidence to show that all controlled documents were issued and/or received
• Donor acceptance documented on the RD by the nurse before the donor signed the RD
• The verification of labelling of the unit and the specimens at bed side were conducted by the same person that labelled the unit and specimens

Manufacturing Control C.02.012

Risk 1 Observations

• A unit of blood was not recalled after it was noted that a high risk question was not completed by the donor on the RD
• A recalled unit could not be traced to its final disposition

Risk 2 Observations

• Certain relevant sections of the GMP are not addressed in the self-inspection program
• Distribution records were not readily available to permit recall of units

Quality Control C.02.014

Risk 1 Observations

• Returned blood components re-issued without verification of the storage conditions while out of the control of the blood establishment

Quality Control C.02.015

Risk 1 Observations

• Establishment continued to use a transmissible disease screening test kit that was recalled by the manufacturer
• Transmissible disease screening testing not performed according to the test kit manufacturer package insert, for parameters that could affect the results
• For testing laboratories (in-house or contract) the systems and controls in place for the proper qualification, operation, calibration and maintenance of equipment, standards, solutions, and records keeping do not assure that the results and conclusions generated are accurate, precise and reliable

Risk 2 Observations

• No corrective action taken further to several occurrences of non-compliance to QC testing
• Transmissible disease screening test kits were used prior to release by QA department
• No trending was performed as a means of evaluating repetitive errors and subsequently implementing corrective actions necessary to prevent future errors

Risk 3 Observations

• Released test kits were observed stored in the quarantine refrigerator
• Daily QC checks were not documented
• Follow-up to an error/accident not performed with all employees involved in the error/accident

Records C.02.020 to C.02.024

Risk 1 Observations

• Records of donations not maintained
• Records of testing not maintained
• Distribution records not maintained.

Risk 2 Observations

• Records of self audits not maintained

Risk 3 Observations

• There was no supervisor sign-off for daily equipment cleaning records.
• There was no date and/or initial
• Incorrect instrument serial numbers referenced in laboratory records

Risk 3 Observations for Source Plasma collected by Plasmapheresis

Risk 3 Observations

• For a positive or reactive test for disease agents specified in the regulations, the unit label was defaced with a permanent marker, however, the unit was not labelled with the caution statement and hazard symbol as required in C.04.413 (3) (a) of the regulations. (C.04.410)
• No written acknowledgment from donors to indicate they were informed of risks to their health associated with participating in plasmapheresis more frequently than once every eight weeks. (C.04.403)