Therapeutic Products Programme (TPP) Responses to Good Manufacturing Practices (GMP) - Questions from Industry (April 27, 2000 Dialogue)

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Therapeutic Products Programme (TPP) Responses to Good Manufacturing Practices (GMP) - Questions from Industry (April 27, 2000 Dialogue) (PDF Version, 118 Kb)
Date: 2000-11-14

(April 27, 2000 Dialogue)

Please Note: The responses to the questions submitted and addressed in this document are based on current information, procedures, and policies which are in place at this time. The Programme is continually updating and revising policies and procedures and as such the information provided in these responses may change.

ORGANISATION / STRUCTURE

Annex

Quality Control/Assurance Unit - One or more individuals designated by, and reporting directly to, management with defined authority and responsibility to assure that all quality assurance policies are carried out in the organization. (Glossary of Terms)

Question

Can the QC be under control of another department other than Quality Assurance?

Answer

The principles of GMP dictate that both QC and QA be independent from Production. This is to ensure that recommendations by QC/QA which relate to safety and/or quality improvement are not superseded by production issues (Refer to: GMP C.02.013).

Annex

The Medical Officer, who is a licensed physician and is qualified by training or experience, shall have responsibility and authority for all medical and technical procedures, including those that affect laboratory personnel and test performance, and for the consultative and support services that relate to the care and safety of donors. The acceptability of donors must be determined by trained qualified staff under the supervision of a qualified licensed physician. (C.02.006, 6)

Question

Is it the TPP's intent that Collections and Laboratory Managers report to the Medical Officer?

Answer

It is not the role of the TPP to determine reporting lines within the company. The TPP Programme reviews the reporting structure according to the GMP. The intent is to assign overall responsibility of "medical and technical procedures" to the Medical Officer who is expected to be qualified by training and experience to oversee these activities, even when Collection and Laboratory Managers do not report to the Medical Officer.

Annex

QC/QA staff must hold a university degree in science or equivalent experience/knowledge directly related to Immunohematology or nursing. (C.02.006, 8)

Question

Please explain the intent of this section. To what level of "staff" is this intended to apply? We request deletion of the restriction of related knowledge/experience to the field of immunohematology or nursing.

Answer

The intent is that all staff have the appropriate qualifications, including experience, knowledge, and training to enable them to perform their specific duties. We recognize that disciplines provided in the Annex are limiting and these will be reconsidered at the next review.

Annex

Within a blood component fabricating operation, the requirements of this section may be fulfilled by positions or departments other than the Quality Control Department as specified in the operating procedures. (C.02.014, 2)

Question

Is this exemption (allowed by the US in the context of small community blood banks) truly appropriate in the context of the current Canadian blood system?

Answer

This is appropriate as long as the staff are adequately qualified and the Quality Control Department is independent of production. The organizational structure is the responsibility of the operator but must comply with the GMP requirements.

Comment: Staffing Changes.

Question

Is it required in 7 days or can it be annual?

Answer

Currently, according to the terms and conditions of an Establishment License, notification of the appointment of a new staff member is required within 7 calendar days. This is under consideration by the TPP.

FACILITIES

Annex

Facilities - Any area, including mobile clinic sites, used for the collection, testing, component production, storage (including records) or distribution of blood and blood components. (Glossary of Terms)

Question

Does storage include storage of supplies?

Answer

Yes. It includes storage of supplies required for the fabrication process.

OPERATIONAL/PRODUCT PRODUCTION

Annex

Directed Donations - Blood collected from an individual for the purpose of transfusion to a different individual, named by the donor, who has been identified in advance to be compatible. (Glossary of Terms)

Question

What level of compatibility is required/intended? ABO/Rh or full cross-match?

Answer

The level of required compatibility is defined by the operators in their approved Standard Operating Procedures.

Annex

Computers, which maintain data used to identify donors, to make decisions regarding the suitability of blood components for transfusion or further manufacture, and/or to maintain data used to trace a unit of blood or a blood component from collection to its final disposition, must be validated in accordance with current Health Canada guidelines (Validation of Computerised Systems in Blood Establishments) prior to implementation and must be maintained in a validated state. (C.02.005, 4)

Question

What is the TPP's position with respect to validation of networks (LAN or WAN) used to support communication of information within or between regulated systems?

Answer

Networks must be validated in conjunction with and relative to the operational applications relying on the network.

Annex

Key personnel shall include at least a Production Manager, a Quality Assurance (QC/AC) Manager and a Medical Officer. An individual may have more than one function but the Production Manager and Quality Assurance Manager must be independent of each other. (C.02.006, 5)

Question

Does the TPP view Donor suitability assessment and testing of donations to be production or Quality control functions? (In general, the drugs GMPs would deem them to be the latter).

Answer

Currently, according to the Annex, donor suitability is considered to be Raw Material Testing and Donor Testing is considered to be Quality Control and it is recognized that donor screening and testing are linked and are used in combination to qualify donors.

Annex

Individuals in charge of production should hold a post secondary qualification (e.g., in management, medical laboratory science, general science or nursing) and have practical experience under professional guidance in the manufacture and control of therapeutic products made under GMP. Individuals with equivalent combination of education, training and experience may be qualified. (C.02.006, 7)

Question

Is a post-secondary qualification in management with no background in science truly adequate for this function?

Answer

Qualifications in management alone, may not be adequate for this function. It is understood that the function would be performed by an individual with the appropriate knowledge, education, training, and experience, this may also include qualifications in management. This will be considered in future revisions of the Annex.

Annex

Blood establishments routinely fabricate blood components in a closed system so that there is no possibility of microbial contamination from outside after collection of the blood from the donor. (C.02.007, 1)

Question

How does this rule apply when talking about a closed system; what is TPP's intent? Please clarify.

Answer

The Sanitation specification listed in the GMP Guidelines does not apply to Blood Establishments. The statement indicated above was included in an effort to explain why this specification does not apply.

Annex

Personnel shall be aware that microbial contamination of themselves, the donors, the blood components and the environment must be prevented. (C.02.008, 2)

Question

We would like some elaboration of this requirement. For example: (a) Would someone with HBV or a cold be medically excluded from working in these areas? (b) Can a Medical Director approve an individual working in any of these areas based on the use of Universal Precautions, such as a mask to prevent transmission of a cold virus?

Answer

Universal precautions are in place to ensure minimal microbial contamination and therefore should be followed at all times. With respect to risks associated with the staff working in specific areas of a Centre, this would be at the discretion of the Medical Officer.

Annex

A comprehensive list of donors who are temporarily or permanently deferred must be maintained. If a blood manufacturer has multiple collection and processing facilities, a composite donor deferral registry, including the names and/or unique identifiers of all donors deferred at each facility, must be made available to each site and updated on a regular basis. (C.02.009, 2.3)

Question

What is TPP's expectation vis-à-vis sharing of information with other manufacturers? (i.e. Cangene)

Answer

The TPP recommends open dialogue and sharing of information between manufacturers. With respect to information about donor deferral the TPP has requested the development of a National Donor Deferral Registry.

Annex

Labelling of blood components (C.02.011, 4)

Question

No mention is made of ISBT code 128 standards. Is it still the TPP's intent to adopt these standards?

Answer

ISBT code 128 standards are intended to be international standards. Once in place, it is TPP's expectation that these labelling standards will be adopted by the fabricator.

Annex

The label shall state the composition and volume of anticoagulant/additive, the Establishment Licence Number and address of the component fabricator, and date of expiry. Expiry labels for products with a shelf-life of 72 hours or less must include the time of expiry. (C.02.011, 4.6)

Question

(a) Is "CPDA-1"or "AS-3" an adequate statement of composition? This approach has been previously approved by BBR.
(b) Is it the TPP's intent to require blood components to carry a DIN? If not, why not?

Answer

(a) Due to restriction of labelling size, abbreviated identification of the anticoagulant is acceptable on the label. The full composition should be stated in the Circular of Information which is an extension of labelling.
(b) No, DINs are in place in order to assist provincial health care drug reimbursement programs. Blood and blood components are exempt from this and therefore it was decided not to assign them DINs. At this time TPP has no plans to assign DINs to blood components.

Annex

The guidance on recalls in the document entitled 'Product Recall Procedures' published by the Health Protection Branch does not apply in its entirety to Blood Components. (C.02.012, 1.4)

Question

What are the exact exemptions? Define "...does not apply to in its entirety to Blood Components".

Answer

To avoid future confusion reference to this document will be removed from future versions of the Annex. The TPP recognizes the need to have specific guidelines for the recall of blood and blood components. In the meantime, fabricators should continue to follow their own approved procedures.

Annex

In the case of C.02.014 (2), if blood components are returned to the manufacturer they are only acceptable for re-issue if the manufacturer can document that the product, while out of their hands, was continuously stored under the appropriate storage conditions. (C.02.014, 6)

Question

Why is the reference to "appropriate" storage conditions rather than to "labelled" storage conditions?

Answer

The approved labelled storage conditions are considered to be the appropriate storage conditions. The Annex will be revised accordingly.

Annex

The donor screening criteria (see Raw Material Testing) and donor sample testing (Quality Control Department) are factors in determining the acceptable quality and safety of blood and blood components. In process controls, as specified in approved OPs, provide specific GMP for Blood Component Fabrication. (C.02.015, 1)

Question

The description of donor sample testing as part of the Quality Control Department seems inconsistent with C.02.006 (6).

Answer

This inconsistency is noted and will be addressed.

Annex

All donors of whole blood must be tested for the following serological tests at the time of each donation:

1. ABO group including forward and reverse grouping
2. Rh group (D and weak D testing)
3. Antibody screen. (C.02.015, 5.3)

Question

1. Is a single test acceptable if the method used has been shown to detect weak D antigens?
2. What is the TPP's criteria for "D" weak?
3. Do donors of RBC for an immunization program require ABO, Rh and antibody screening at every donation?

Answers

1. A single test is acceptable, provided that there is evidence to indicate that the method used has been validated to detect weak D and that this is reflected in the reagent package insert.
2. TPP considers weak D positive red cells to be those which require longer incubation with the Anti-D reagent or the addition of antiglobulin serum after incubation in order to be detected.
3. Yes. Donors of red blood cells for an immunization programme do require ABO, Rh and antibody screening at every donation.

Annex

All donors must be screened for the following transmissible disease markers at the time of each donation:

• Syphilis
• Hepatitis B surface antigen (HBsAg)
• Antibody to Hepatitis C virus (HCV)
• Antibody to HIV type 1 and 2
• Antibody to HTLV-I/II (except plasma for further manufacturing use only)
• HIV-I p24 Ag
• Any disease marker(s) specifically required by the Minister (C.02.015, 5.4)

Question

Note: Addition of HTLV I/II and HIV-1p24 is inconsistent with 1992 Guidelines for Blood Collection and Blood Component Manufacturing (this Annex does not clearly indicate the status of these Guidelines). Clarify that source plasma donors do not require syphilis and HTLV I/II testing at each donation.

Answer

At this time the 1992 Guidelines are still applicable, however information in the Annex is considered to be more current. The two documents should be used in conjunction until such times as all documents providing fabrication guidance on blood are integrated.

In regards to donors of plasma for further manufacture:

1. Currently, testing for syphilis is required every three months.
2. Testing for HTLV I/II is not required for plasma intended for further manufacturing.

Annex

All donors that are found repeat reactive for a transmissible disease marker listed above [C.02.015, 5.4] must be deferred. (C.02.015, 5.6)

Question

Is there a possibility of a reintegration protocol based on confirmation testing?

Answer

Yes, the TPP would review and examine the acceptability of any reintegration protocols that a manufacturer/ fabricator may submit.

Annex

A quality control program which assesses the quality of all manufactured blood components must be followed by every fabricator. The frequency of quality control testing, expressed as a percent of overall production, as well as the minimum number specified over a period of time, and the acceptable criteria for quality control testing of each type of component must be established by each fabricator. (C.02.015, 6)

Question

How does TPP define quality control for a specialty plasma Centre manufacturing source plasma for further manufacturing?

Answer

Donor suitability, including negative test results for transmissible disease is established prior to release of the plasma unit for further manufacturing. The only additional requirement is visual inspection for the integrity of the unit. Other quality control requirements may be dictated by the nature of the fabricating process.

Annex

Records of sanitation need not be retained. (C.02.024, 2)

Question

This exemption is inconsistent with general requirements for the drug industry. Is it the intent to exempt these records from indefinite retention?

Answer

Sanitation does not present with the same relevance in Blood Establishments as in Pharmaceutical Drug Fabrication, therefore there is no need to keep records of routine facility cleaning procedures. However, records of spill/accident clean-ups and any equipment cleaning required during the fabrication process must be documented and retained with the production records. This will be clarified in the next addition of the Annex.

Annex

Although blood is not a sterile drug, sterility testing should be performed as part of Quality Control testing. Sterility testing must be done with a methodology specific to aerobic and anaerobic pathogens in blood. Sterility testing serves as a monitor of the effectiveness of the protocol for phlebotomy site preparation. (C.02.015, 8)

Question

Is it the TPP's intent that only the presence of pathogen organisms (in contrast to normal skin flora) be considered? Sterility testing may serve as a monitor (rather than "Sterility testing serves"....) would be more accurate.

Answer

It is not the intent to test only for pathogen organisms. The next version will be revised to clarify the intent.

DEFINITIONS

Annex

A blood establishment shall be under the direction of designated, qualified personnel who shall exercise control of the establishment in all matters relating to good manufacturing practices (GMP) for blood component manufacturing. Designated staff shall have an understanding of the science principles and techniques involved in the manufacture of blood components. Training and competency evaluations must be documented. (C.02.006, 2)

Question

Please define the term "blood establishment" so that we can put this requirement in the proper context.

Answer

A "Blood Establishment" is the premises/buildings/remote sites where the fabrication (collection, production, processing), packaging/labelling/, testing and/or distribution of blood and blood components takes place.

Annex

The fabricator shall ensure the employment of adequate personnel qualified by education and/or experience, as specified in their job descriptions. The tasks and responsibilities of all individuals must be clearly understood and documented. All personnel shall be trained in the principles of GMP relevant to their work. Records of the qualifications, training, and continuing competence of individuals shall be maintained. (C.02.006, 3)

Question

Is the intent of the term "fabricator" different from that of "blood establishment" in item 2 (previous question)

Answer

Yes. The term "fabricator" refers to the manufacturer, operator, company or firm responsible for fabricating/ manufacturing/ producing the product. A fabricator performs the activity of fabrication (see the definition provided in the next question) which is only one of the licensable activities that may occur in a blood establishment (see response to the previous question for licensable activities). The blood establishment is the facility or premises at which the licensable activities take place.

Annex

A quality control program which assesses the quality of all manufactured blood components must be followed by every fabricator. The frequency of quality control testing, expressed as a percent of overall production, as well as the minimum number specified over a period of time, and the acceptable criteria for quality control testing of each type of component must be established by each fabricator. (C.02.015, 6)

Question

Please define the term "fabricator" in contrast to the term "operator" used elsewhere in the Annex.

Answer

The term "Fabricator", as addressed in the previous question, refers to the manufacturer, operator company or firm responsible for fabricating/manufacturing/producing the product. The term "Operator" is a unique Programme term to describe the role of Canadian Blood Services and Héma-Québec, which is synonymous with fabricator.

Annex

Contract facility - Organization performing work associated with the manufacturing process for the manufacturer. (Glossary of Terms)

Question

Is this term applicable only to organizations external to the "manufacturer"?

Answer

A contract facility is considered to be external to the fabricator/manufacturer.

Annex

Processing - Any fabricating step performed between the collection of blood and the issuing of a component. (Glossary of Terms)

Question

Why is donor screening excluded? What is the difference between "processing", "fabricating", and "manufacturing"?

Answer

"Processing" is synonymous with the term "fabricating" and "manufacturing". Accordingly, fabricating includes all steps from donor selection to final disposition of products. This will be clarified in the next version of the Annex.

Annex

Sub-Centre - Permanent site under the control of a Blood Centre, which is licensed for limited fabrication activities. (Glossary of Terms)

Question

Fixed sites are not defined and are regulated differently from sub-centres.

Answer

Definitions will be added to the next edition of the Annex to clarify this issue. Fixed sites are not regulated differently. Regulation remains the same, regardless of the site of operations.

Annex

Adequate storage space for the dry, clean and orderly placement of stored materials under monitored temperature conditions compatible with conditions specified on label. Storage areas shall provide for suitable and effective separation of quarantined and released material. (C.02.004, 3.12)

Question

What does the term 'stored material' include? Does it refer to soft goods, equipment, labels, blood products or everything at a collection centre?

Answer

The term 'stored material' includes all equipment, soft goods, labels, etc. used in the fabricating process.

Annex

Procedure(s) to detail the receipt, inspection, and storage of material and products within the premises. (C.02.011, 1.4.17)

Question

Requires clarification regarding the use of the term "material". Does this mean blood products, soft goods or both?

Answer

The requirement refers to all goods and materials used that would impact on the quality of the product, as well as the products themselves.

Annex

Individuals in charge of production should hold a post secondary qualification (e.g., in management, medical laboratory science, general science or nursing) and have had practical experience under professional guidance in the manufacture and control of therapeutic products made under GMP. Individuals with equivalent combination of education, training and experience may be qualified. (C.02.006, 7)

Question

The term "production" is not defined.

Answer

The term "production" is defined in the GMP Guideline's in the Glossary of Terms section as: All operations involved in the preparation of a finished product, from receipt of materials, through processing and packaging, to completion of the finished product, including storage.

Annex

There must be a system in place to ensure the timely reporting of complaints or product defects to the vendor and prompt effective remedial action by the vendor. (C.02.010, 1.2)

Question

Please define the term "complaint" in this context.

Answer

Any issue of concern or dissatisfaction raised by a customer/client.

Annex

Packaging Material testing does not apply to blood component manufacturing as original collection bags and satellite bags must be approved Medical Devices. Additional routine testing is not required for use of approved collection bags. However, testing may be required during an investigation of a complaint or an adverse reaction. (C.02.016 and C.02.017, 1)

Question

See comments under C.02.009 (3). Please define complaint.

Answer

Any issue of concern or dissatisfaction raised by a customer/client.

Annex

Each donation shall be identified in a unique manner and shall allow for the traceability of each blood component back to the donor and forward to final disposition. (C.02.011, 4.3)

Question

What is meant by "final disposition" particularly in reference to destruction of units? (see also "point of end use" - C.02.021 (2).

Answer

The final disposition refers to the products' final use or destruction. If destruction of the product is conducted by a contractor for the fabricator, then confirmation of destruction should be supplied to the fabricator, and records retained.

Annex

Records that substantiate the safety of blood and blood components and the traceability of the components from donor to final disposition shall be retained indefinitely. The records must enable the fabricator to trace blood or blood components to donors in the case of a traceback investigation, and to the point of end use in case of lookbacks. (C.02.021, 2)

Question

What is done with the final disposition of discarded products? Is there a clear/ consistent procedure on what we request to see at the Centres. How far do they need to go, to the contractor, or do they have to go a step further to the confirmation of destruction by the contractor, to the actual bin etc.?

Answer

The final disposition refers to the products' final use or destruction. If destruction of the product is conducted by a contractor for the fabricator, then confirmation of destruction should be supplied to the fabricator, and records retained.

Annex

A sample taken from every final product processed in an open system (e.g., red blood cells, deglycerolized) shall be tested retrospectively for sterility. (C.02.029, 4)

Question

Explain 'retrospectively'.

Answer

Sterility testing results may not be available prior to use or transfusion of the component, due to the required incubation time frames.

Comment: SOP - Standard Operating Procedure.

Question

What is meant by validation of SOPs? What is it? Do you validate SOPs or do you validate the process?

Answer

SOP validation is the process by which a new SOP or a revised SOP is assessed to determine that the work instructions provided are accurate, clear and understandable to staff and reflective of the process which it describes.

Annex

Autologous Donation - Blood collected from an individual for the purpose of transfusion back to the same individual. (Glossary of Terms)

Question

Are they considered as patient care? Should Medical officers have the final word on the eligibility of donors and the suitability of the components? Are the standards for autologous donations different from those for homologous donations, if so how should they be handled?

Answer

As a result of the special circumstances associated with autologous blood donations, donor-patient safety is of particular concern and dictates the requirements under these circumstances. Suitable guidelines for autologous donations must be established by the Medical Officer and documented in the establishment's procedures manual. Decisions regarding autologous donations are often taken in consultation with the donor-patient's physician. In this context, standards for autologous donations are different from those for homologous donations. However, many requirements for homologous donations, such as collection, storage and transport, also apply to autologous donations.

Comment: Some people think that Lotus or Excel are regulated computer systems.

Question

What is BBR's definition of a regulated computer system?

Answer

The systems are not regulated, however the function of the system and data generated in a specific process may be regulated.

COMMENTS

Annex

Post Donation Information (PDI) - Information related to a donor or a donation made available to the collection facility following a donation. The information can be provided by the donor or other source. It may adversely affect the safety and/or quality of donated blood/component. PDI does not include errors, accidents or anomalies that occur during screening or later during collection, processing or testing but are discovered at some point after the donation is made. (Glossary of Terms)

Question

PDI may "indicate that the safety and/or quality of the donated blood component is compromised". Information cannot directly affect quality.

Answer

The information received as PDI could relate to a risk that may affect the safety and/or quality of the donated blood and thus "indicate that the safety and/or quality of the donated blood component is compromised". In the next addition of the Annex this will be more specific.

Annex

Processing - Any fabricating step performed between the collection of blood and the issuing of a component. (Glossary of Terms)

Question

For the whole document: Use of consistent terminology would be appreciated.

Answer

In the revised version of the Annex, every effort will be made to use consistent terminology.

Annex

When blood collection clinics are conducted by mobile teams, a realistic attitude towards environmental standards is necessary. The premises should satisfy common sense requirements for the health and safety of both the mobile teams, and the donors concerned, with due regard for relevant legislation or regulation. Points to check should include adequate heating, lighting and ventilation, general cleanliness, provision of a secure supply of water and electricity, adequate sanitation, compliance with fire regulations, satisfactory access for unloading and loading of equipment, adequate space to allow free access to the bleed and rest beds. An area shall be provided for a confidential interview with a donor. (C.02.004, 4)

Question

1. These requirements do not appear to address the security of supplies or units.
2. References such as "common sense requirements" do not provide clear guidance for manufacturers in support of maximizing the quality, safety, purity security, identity and potency of finished products.

Answer

1. This will be addressed in the next version.
2. In addition, references such as "common sense" will be replaced and specific guidance will be provided.

Annex

The collection bags, which are approved Medical Devices, do not require further testing. The certificate of analysis for each lot of collection bags must be reviewed and approved prior releasing for clinic use. Each collection bag must be visually examined prior to its use for blood collection, again at the time of product release into available inventory, and finally before the released product is distributed. (C.02.009, 3)

Question

Given the critical nature of the collection bags, these should be subject to lot release by Medical Devices. This should include confirmation that the materials and construction of the actual containers, filters and their composition, and the sterility of any solutions contained meet pre-determined specifications.

Answer

Overall responsibility of safety and efficacy requires efficient communications between users and manufacturers, including complaint handling, required modifications to materials, design, indications for use. Currently blood bags are classified into risk class II, including leukoreduction filters. If additional information is provided to the MDB to merit classification into higher risk category this would be considered.

Annex

Because of their intended use, good quality is crucial to blood components. Therefore, the collection of blood and the processing, storage and distribution of blood components must be organised in a way to ensure a high component quality. This can only be achieved if the fabricator has a system of quality management. Quality management is an integrated system of quality assurance covering all matters which individually or collectively influence the components in order to guarantee their quality. (C.02.014, 3)

Question

We agree with this comment. It supports our comments regarding C.02.009 (3) and C.02.016 and C.02.017 (1).

Answer

No response required.

CORRECTIONS / REVISIONS

Annex

Computers, which maintain data used to identify donors, to make decisions regarding the suitability of blood components for transfusion or further manufacture, and/or to maintain data used to trace a unit of blood or a blood component from collection to its final disposition, must be validated in accordance with current Health Canada guidelines (Validation of Computerised Systems in Blood Establishments) prior to implementation and must be maintained in a validated state. (C.02.005, 4)

Question

Cannot locate "current Health Canada guidelines (Validation of Computerised Systems in Blood Establishments)" Document currently in use is "Guidelines for Computerised System Validation" prepared by Outer Join Developments.

Answer

TPP regrets that the incorrect document was quoted in the Annex. Currently, new guidelines are being developed and when available will be distributed to all manufacturers for discussion and consultation.

Annex

Hygiene instructions, including clothing and behaviour requirements, must be present in each department. These instructions should be understood and followed by all personnel. (C.02.008, 3)

Question

Define 'behaviour requirements'.

Answer

In the next revision of the guideline, 'behaviour requirements' will be revised to be more specific.

Annex

If coloured labels are used to identify products for transfusion, the colours must follow the conventions outlined in the guidelines for Blood Collection and Component Manufacturing (Part IV section 2.4.2). (C.02.011, 4.4)

Question

Translation problem - French document does not state "if coloured labels are used..." , just states "coloured labels have to conform..."

Answer

This will be corrected.

SUBMISSION RELATED ISSUES

Comment: Response regarding "known" time lines re: categorization of SOPS considered incorrect. Example - Defer Donor SOP received a Category 3 rating and three (3) days later correspondence received approving its implementation.

Question

How are we to plan and use resources appropriately when this type of situation occurs?

Answer

The assignment of categories to licence amendment submissions is an integral part of the risk management approach adopted by the TPP. The TPP has assigned performance targets associated with each submission type. These targets have been put in place in an effort to manage programme workload and to provide the sponsor with a time frame of when to expect a submission to be reviewed. However, workload and staff availability do impact the process and sometimes submissions may be reviewed well within targets or may not meet the target time.

Comment: Bug Fix vs Change.

Question

Do both need a five (5) part submission requiring pre-approval?

Answer

It is the manufacturers responsibility to submit a submission which contains the necessary information to review the proposed change(s). In order to assist this process, guidelines are produced by the Programme. Currently, it is recommended that manufacturers refer to the "Process for License Amendment". As new guidelines become available, manufacturers will be informed.