This section discusses typical regulations and standards related to validation in the TS. Although specific guidelines and requirements vary by country, there are commonalities that apply globally.
- Standards vs. regulations
- Validation regulatory requirements
- Audit deficiencies
- Self study questions
- Further Reading
Before discussing validation requirements per se, it is worthwhile to recall that standards and regulations, while similar, do differ in significant ways. Below are examples of country-specific standards and regulations relevant toTS.
Standards are voluntary norms of behaviour and best practice, which in and of themselves, are not legislative tools. To have the force of law, standards must be incorporated into government regulations. Regardless, TS strive to follow standards because
- Standards are in the interest of patient safety and patient safety is paramount
- Standards constitute best practice and TS take pride in being current and following best practices
- Law suits involving negligence typically use both peers and standards to assess if an action was negligent
- Standards are used for laboratory accreditation by some government agencies.
Examples of country-specific standards:
Australia and New Zealand. ANZSBT provides best practice guidelines.
Canada. The CSTM maintains CSTM Standards for Hospital Transfusion Services, which TS are encouraged to adopt as best practice and which are used by several provinces as the basis for TS accreditation. CSTM Standards do not apply to blood suppliers. Where applicable, CSTM Standards are referenced to CSA Standard Z902-04, which applies to both blood suppliers and hospital transfusion services. CSA Standards are not regulations but Health Canada encourages health organizations to follow the practices in the CSA Standards as they represent the current industry standard for safety.
UK. The BCSH provides guidelines for best practice.
USA. The AABB has Standards that are used for voluntarily accreditation by the AABB and are widely accepted as best practice.
Regulationsapply standards through the force of law and provide penalties for noncompliance. Some examples:
Australia. The Dept. of Health and Ageing regulates the manufacture of blood, blood components, plasma derivatives, medical devices, etc.
Canada. Health Canada is the regulator and currently has GMP regulations that apply to blood suppliers but not transfusion services, as well as other legislation that regulates medical devices, LIS, etc. Regulations that will apply to transfusion services are being developed using CSA Z902-04 and other resources.
UK. As a result of the EU blood directive, the UK has new legislation, The Blood Safety and Quality Regulations 2005, which applies to both blood establishments (UK Blood Services) and hospital transfusion services.
USA. The FDA regulates the manufacturer of blood, blood components, medical devices, LIS, etc., through a vast network of regulations and guidance for industry.
Both regulations and standards relevant for TS are included in the following discussion, with a focus on Canada. Requirements for other countries are similar but not necessarily identical. Readers are encouraged to consult applicable resources within their own countries.
Validation - the process of proving and documenting that something works the way it is supposed to work - is a key part of a quality system. Current standards and regulations for TS are based upon a quality system approach, a critical component of which is process control, and thus standards contain numerous requirements for validation.
In Canada CSTM Standards for hospital transfusion services include validation standards for
- recipient and blood product identification
- operating procedures
- transfer of records to storage media
- information systems
- equipment, including storage equipment
- semi-automated and automated instruments for ABO and Rh testing and antibody detection, and
their auxiliary equipment
- shipping containers
- washing red cell components
An example from the CSTM standards:
- D7.4.1 Semi-automated and automated instruments for ABO and Rh testing and their auxiliary equipment shall be validated to perform with absolute equivalence to manual validated ABO and Rh typing methods.
- D7.4.2 Semi-automated and automated instruments for antibody detection and their auxiliary equipment shall be validated to perform with substantial equivalence to manual validated antibody screening methods.
- D7.4.3 Semi-automated and automated instruments and their auxiliary equipment shall be validated to ensure absolute positive identification of specimens and testing results.
As shown in case background, validation-related deficiencies are common when laboratories are audited.
- You have no written protocol requiring or describing the validation of the [redacted] ABO/RH machine, including accept/reject criteria, number of samples per run, stress testing, and investigations of samples classified as ?Invalid? by the blood bank computer system.
- Some of the validation test results for the [redacted] analyzer, including some of the raw data, were missing or unavailable for review during the inspection.
- The response is inadequate, in that the "validation" data lacks specific details regarding the steps taken to qualify the equipment.
The case background provided a few examples of deficiencies that inspectors found while auditing transfusion services and other facilities. Once cited, organizations are required to provide responses that address and correct the deficiencies.
Places to find examples of audit citations and their responses include
- Canadian Blood Services: actions in response to Health Canada observations
- Note: Most CBS observations do not relate to validation and other quality system deficiencies
- FDA warning letters and responses
A review of audit citations, reading related literature, and consultations with colleagues reveal many obvious examples of validation deficiencies such as failing to validate equipment and methods. But a review also shows that some basic elements in the validation process may inadvertently get missed or be done inadequately. Here are a few of the basic that sometimes get missed:
Documentation. Not only must processes, methods, equipment, etc., be validated, there must be detailed documented evidence to prove that they were. Documentation is a key part of validation, as shown in its definition:
- The establishment of documented and objective evidence that the particular requirements for a specific intended use can be consistently fulfilled 1
Besides the details documented in validation SOPs, master plans, protocols, and reports, detailed documentation requires that all raw data from validation experiments must be retained for possible review by auditors.
Strategies for handling validation deficiencies. The validation process must include includes plans for what to do when methods, equipment, etc., do not meet acceptance criteria. Corrective action and its verification must also be documented, for example by using a validation deficiency report. Such a reportdescribes the particular deficiency, its likely cause, impact, corrective action, verification, and approval.
Review and Approval. Validation master plans and protocols must identify staff responsible for all validation processes. The final validation report must also show evidence that the validation has been approved by senior management.
Help with Accreditation
Accrediting organizations and governments provide guidelines to help organizations meet required standards and regulations. Besides government guidelines (Health Canada, UK Dept. of Health, U.S.FDA, etc.), many other resources are available. Some examples:
- Canada (many free resources)
Validation deficiencies remain common in countries such as the USA where TS have been audited against quality systems for some time. Now that other countries are implementing TS regulations and standards based on quality systems, resources are needed even more to help TS with validation processes.
1. What is the key difference between standards and regulations?
2. What are some of the reasons why TS should follow standards?
3. Why is validation such an important part of blood safety standards and regulations?
- Part 1: Introduction to terminology
- Part 2: Types of validation
- Part 3. Determining when and how extensively to validate a method
- Part 4: Regulations and standards <--You are here
- Part 5: Validation examples (tools and resources)
1. UK Government. The Blood Safety and Quality Regulations 2005