Question 2005-02

We were informed by the FECC that "on October 30th 2005, GMP becomes mandatory for distributors of pharmaceutical starting materials" Apparently it is becoming EU legislation on that day. Do you have any more information on this? The FECC are running a seminar on it in Brussels in November, part of the agenda is "Good Practices in the Active Pharmaceutical Ingredients Supply Chain. How to comply with ICH Q7A”. As far as I am aware, the GMP guide we follow as part of PS 9100 is consistent with ICH Q7A. Will our standard cover the new EU guidelines? After digging a bit, I think the directive is 2004/27/EC.

http://pharmacos.eudra.org/F2/eudralex/vol-1/home.htm

http://pharmacos.eudra.org/F2/eudralex/vol- /DIR_2004_27/DIR_2004_27_EN.pdf .

I am concerned that this is the first I have heard of this. Obviously (I hope) it isn't an issue for us as we have PS 9100:2002. However, when we found out about this at the ESAD II conference yesterday, a lot of chemical distributors were concerned. Do you know anything about this?

Answer

The Directive 2004/27/EC is the correct standard to consider but it has to be read together with the original directive 2001/83/EC, which it amends.

This directive will have relevance to manufacturers and distributors of Active Pharmaceutical Ingredients (APIs) and some excipients in the future and the UK legislation to effect this is SI 2005/2789. The date of 30 th October 2005 in the directive is the one by which national governments are directed to implement national legislation and whilst some governments are understood to have met this deadline, some have not yet done so. The consequence of this is that distributors must understand the actual requirements in each country they supply and meet the legislation where it exists.

The actual requirements of concern are defined in clauses 33 & 34 of 2004/27/EC, which amend articles 46 and 46a of 2001/83/EC. This requires that manufacturer’s of APIs and distributors, who repackage or re-label an API, must follow appropriate GMP (ICH Q7a as included in EU GMPs Annex 18). This does not of course mean that all distributors must follow ICH Q7a.

There will be an additional requirement for manufacturers of certain excipients to also meet GMP principles, which will be less stringent than ICH Q7a. The GMP principles and the list of the ‘certain’ excipients are now being defined by the EC with input from regulators and industry representatives. PQG are represented in these discussions and the new draft IPEC/PQG guideline for Excipients GMPs (to be launched February 2006) is a key source document for the GMP principles. The list of certain excipients is likely to include the TSE materials, Human derived materials, sterile excipients, and possibly glycerine and propylene glycol. Industry is in general agreement with the regulators and the EC except with glycerine and propylene glycol being on the list. This is because industry believes the problems which have occurred with them, historically were due to criminal activity and this issue would not be resolved by GMP. Whether the principles of GMP should cover distribution of excipients as well as manufacturing is still being discussed by EC lawyers.

You also raised a question relating to PS 9100 i.e. ‘Is this a suitable standard?’ In our opinion, it is suitable as it is covers all elements of ICH Q7a as applicable to excipients. The regulatory expectations for excipients GMP are still being defined by the EC. It is expected there will be mandatory broad principles of GMP, which are less stringent than ICH Q7a, and will be in line with PS 9100. PQG recognise that suppliers and distributors require GMP to be in a format that meshes with their existing Quality Management Systems, which are invariably based on ISO 9001. As you know PS 9100 meets this need.

return to top of page

Question 2005-01

I am having a problem with regard to a certification body’s interpretation of the PS 9000 standard and I am looking for advice as to whether they are interpreting it correctly or not.

My question relates to section 10.1 and 10.1.2 of the standard. My client produces leaflets and has only one customer that uses pharmacode. Unfortunately their on-line scanners have recently become faulty and the cost of repairing them is considered inhibitive due to the low volume of this work. The certification body is insisting that that they must carry out a validation using on-line scanning. Can they do this? Is it possible that the customer could issue a concession (indicating they the customer will carry out the validation)? Or can a random sample be taken and tested with a hand scanner or similar as an alternative?

It is likely long term that Pharmacode will be phased out by this customer, so will it be necessary to remove the on-line scanners or can they just disable them?

I know common sense should prevail in this case, but the certification auditor seems to be extremely inflexible.

Answer

If the code has been included in the design by the customer for security purposes then each item must be verified Clause 10.1.1 refers to documented approval by the customer before product release, and this is the key point, Meeting customer requirements would be the overriding factor here and, if the customer can accept responsibility for 100% verification of the bar code (or perhaps has other methods of control), and this is documented, then the principles of PS 9000 can be met. Equipment breakdown would not be considered as a good reason for not complying with an important requirement of PS 9000. The redundant scanners should be removed if at all possible, otherwise clearly indicated as not in use.

There are situations where security barcoded verification on-line (PS 9000 10.1.2) is not always possible, such as with leaflets (and other packaging components). In some cases, this is due to design and positioning; in others ‘read-through’. In these cases, formal agreement is required with the client (customer).

In summary, it is down to common sense and customer agreement although extra care and other, appropriate checks may need to be made. A documented risk analysis should be carried out and action taken to ensure the security of the work concerned. In this case, if there is a documented agreement with the customer to omit barcode verification, the 3 rd Party Certification auditor should be able to accept it.

return to top of page

Question (2004-04)

Whilst reviewing internal systems within our operation a concern has been raised as to the definition "3.24 Origination" where it states that: - Origination is all preparation activities prior to print. These include concept design, graphics, reprographics, film, plate making, silk screens and digital files and masters. The concern is that the definition states areas such as plate making and silk screens, and by definition the process should be subject to a recorded line clearance as stated under 9.1.7. I also feel this conflicts with section 11, as plates production should form part of section 12 therefore is not consistent with the definition. In todays technology this would be both impractical and not workable as plates are generated through both conventional means and computer to plate (CTP), which in the case of CTP are made on a multiple basis, and to carry out a line clearance as per 9.1.7 would seriously create issues within manufacturing environments. As a contributor to both PS9000 & PS9004 I would request a statement to be sort from PQG and would recommend that the plate production process be subject to a risk assessment rather than a formal line clearance.

Answer

PQG accepts that p Processes will change with new technology and PQG accepts this,but operational use must incorporate practices compliant with key quality objectives of product security and integrity. Computer to Plate (CTP) technology differs from conventional plate making in that it is a continuous not a discrete batch process with no facility for stop start routines to allow batch – batch line clearance practices.

The process has similarities with modern changeover systems (see PS 9000 reference 13.2 "changeover systems that....do not permit a total line clearance, shall be subject to a documented risk assessment and operated with controls to ensure product security").

Some new technologies are already covered in PS 9000, (e.g. digital printing, reference 10.7, which states "new activities...shall be controlled and documented to ensure accuracy and security of the product").

• On the basis that CTP is 'new' (in that it is not covered by PS 9000), then new processes must be subject to a risk assessment (see PS 9000 reference 3.31), to identify real and potential quality risk area's and the necessary operational controls to prevent risks of mix-ups, e.g. in the artwork files, plate identification, separation, segregation and containment of completed plates.

A flow diagram, as shown, facilitates an understanding of the new process and a comparison with the old. In key areas, documented operational double checks are needed, e.g. at collation of each set of plates prior to transfer to the print line. Validation of the final process will need to be supplemented by internal audits showing that the quality process is effective. Other references are PS 9000: 4.2.3:7.3.1; ISO 9004: 7.1.3.3.

return to top of page

Question (2004-03)

Our Company designs and manufactures filtration products for the pharmaceutical industry. We have been subject to a number of audits by pharmaceutical companies whose auditors utilise PS 9000. As a result of these audits we have subsequently built in the GMP elements of PS 9000 into our QMS. We have asked our Certification Body if they can provide a Certificate to PS 9000 although we do not manufacture pharmaceutical packaging products. This enquiry was then referred to the PQG.

Answer

For the products referred to (i.e. filters), the PQG do not see any reason why a PQG Recognised Certification Body should not offer certification to the PS series (PS 9000:2001 or PS 9100:2002).  Those clauses related to production processes which are not relevant to the client’s products, can be classified as exclusions from ISO 9001:2000 clause 7.  In addition, in the case cited, PS 9000, clauses 10-13 which relate to printed packaging materials could be excluded.

For filtration products, PS 9100 may be a more suitable Standard particularly as it contains more detailed GMP guidance.

Providing a PQG Recognised Certification Body is willing, and has the necessary auditor competence, they can proceed on this basis without reference to the PQG.  Reference to the PS 9000 series should be in the 'Scope' of the Certificate; PS 9000 series documents should not be referred to as 'Standards' alongside ISO 9001:2000 in UKAS Accredited Certificates.  However, if the client and the Certification Body agree, Unaccredited Certificates can be issued referring to PS 9000 or PS 9100 as the 'Standard' (either Certificate is acceptable to the PQG for recognition purposes).

Following Certification to PS 9000 or PS 9100, formal recognition by the PQG as a PS series Certified Supplier, can be granted by applying the PQG Recognition Process. 

See also FAQ 2004-01

return to top of page

Question 2004-02

What is the minimum period for which samples of packaging materials must be retained by suppliers?

Answer

In reaching a sensible and mutually acceptable period for retention, a number of factors need to be considered:

• It is the holder of the Marketing Authorisation (MA) that has responsibility for dealing with long term problems of material deficiency, so the onus rests with them for a supplier/customer agreement on any special retention period.
• The MA holder needs to determine the hazards inherent in an item and assess the risks to the user should a failure occur.
• The Customer should determine if the 'sample' of 'packaging' is regarded as a 'record'. If so, the retention period is 5 years or as otherwise specified by the customer (PS 9000:2001 clause 4.2.4). Record (ISO 9000:2000, 3.7.6) is defined as 'document (3.7.2) stating results achieved or providing evidence of activities performed'. A document is 'information and its supporting medium' - depending upon the circumstances, this could well then include 'samples'.
• It may not be viewed as sensible to store items that take up a large volume, such as 1 litre bottles, at two premises for a lengthy period.
• It would seem sensible for the supplier to keep a 'sheet' sample, (showing all print stations), for a year. This allows for a period use of the item, supply into the market and feedback regarding, for example, complaints about poor adhesion, print removal or substrate deterioration.
• In deciding on an appropriate retention period, the pharmaceutical manufacturer will need to consider the combined set of samples stored at their own and suppliers’ premises, to ensure that they will always have sufficient available to satisfy any investigation.

Although the terms ‘reference samples’ or ‘samples’ may be found in PS 9000 clauses 7.3.5, 7.5.4, 8.2.4 and 13.3, no mention is made about the time for which such samples should be retained: note that paragraph d) of clause 7.2.1: ‘Determination of requirements related to the product’ allows for the customer to specify ‘any additional requirements’

Note that the proposed Annexe 19, to EU GMP, on this subject provides a useful and logical benchmark position, when it specifies in clauses 2.2 & 2.3, that pharmaceutical manufacturers should keep reference samples of primary and printed packaging materials to enable an investigation ‘relating to a labelling/packaging query’. This implies a period of at least the shelf life of the product.

The period of retention then is clearly a matter for agreement between the supplier and their customer and should reflect the nature and criticality of the items being considered, and any implications arising from current regulatory statements.

A decision tree follows with guidance notes to help users.

 

No	Comment
1	It may not be practical or safe to store items, e.g. those that take up a large volume, such as 1 litre bottles etc.
2	Document the decision in your Quality Management System, and communicate your policy to your customers, as necessary.
3	It is the holder of the Marketing Authorisation (i.e. your customer) that has responsibility for dealing with long term problems of material deficiency, so the onus rests with them for a supplier/customer agreement on any special retention period. They need to determine the hazards inherent in an item and assess the risks to the patient should a failure occur, and then notify you accordingly. In deciding on an appropriate retention period, the pharmaceutical manufacturer will need to consider the combined set of samples stored at their own and suppliers' premises, to ensure that they will always have sufficient available to satisfy any investigation. Hopefully it is a sensible interval!
4	Document the decision in your Quality Management System, and communicate your policy to your customers, as necessary.
5	Although the terms 'reference samples' or 'samples' may be found in PS 9000 clauses 7.3.5, 7.5.4, 8.2.4 and 13.3, no mention is made about the time for which such samples should be retained. In these circumstances document your retention period in you Quality Management System and justify the interval. For example, prior experience, other standards or markets may have defined an interval which you have adopted. As appropriate communicate the interval to your customers.

Question (2004-01)

Can the PQG recognise suppliers to PS 9000 and PS 9100 whose products do not exactly fit the title e.g. i) a packaging material supplier to the medical device industry ii) a packaging material supplier to the cosmetics or food industry iii) a supplier of origination (digital files or even old fashioned artwork) to the pharmaceutical industry iv) a raw material supplier of API's v) a raw material supplier to the food industry vi) a supplier of (biological) media to the pharmaceutical industry

Answer

Whilst PS 9000 and PS 9100 are primarily standards for suppliers of pharmaceutical packaging materials and pharmaceutical excipients, the PQG support the use of these standards, and the Good Manufacturing Practices they contain, for related industries and materials.

Furthermore, the PQG will recognise those suppliers who achieve certification against these standards, in accordance with PS 9000 Annex E and PS 9100 Annex B, and award the IQA/PQG Certified Supplier status.

return to top of page

Question (2003-06)

In the PS 9000 book on page 1, the ISO 9001:2000 states that the word 'NOTE' is as follows. Information marked Note is for Guidance in understanding or clarifying the associated requirement. Is this the same definition for the use of a NOTE used in PS 9000?

Answer

This appears to be 'mistake' or proofreading error, there is no reason for 'NOTES' on page 116. In the text, it is all written as 'requirements', i.e. SHALL. If it was a NOTE, it should be written with 'SHOULDS'.

return to top of page

Question (2003-05)

We are looking to get BSi in later this year to get us up to PS 9100 registration. We intend this to be at Foundation level for the entire site. But we have a couple of products where we can meet Intermediate level. Can this mixed approach be accommodated? For example by stating in the scope of registration which products are covered? I ask because I know the design team did not consider this aspect and I think it needs to goto the Partners team formally for consideration.

Answer

Yes, a mixed approach can be accommodated within the scheme. The GMP level(s) should be included in the scope proposed by the organisation, and confirmed by the certification body. It is also a requirement of clause 4.2.2 of PS 9100 that the level of GMP to be applied is defined in the supplier's Quality Manual.

return to top of page

Question (2003-04)

9.1.2 Interior surfaces - are hospital style floors and walls required? We currently have building block walls, which are well maintained, but cannot be described as being smooth. Floor is in need of refurbishment, but standard seems to suggest a coat of paint will not be sufficient?

10.2 Reel fed materials. Paragraph would suggest that some automated missing colour/text detection equipment is required. Do I read this correctly? Can you advise?

Answer

9.1.2 Hospital style surfaces for walls and floors are not required for printing operations. What is being defined here are baseline requirements irrespective of whether the components are product contact or secondary. Clearly what matters is whether the walls can be effectively cleaned. To assess this requires an examination of the walls to look for loose debris or damage. Damaged walls could certainly give rise to contamination. Loose debris may mean the walls are not smooth enough. A similar self-assessment could be to answer the question 'Will a damaged but repainted floor be acceptable?' i.e. The question to be asked would be 'Will we be able to clean this surface effectively if we do not repair the damage before we repaint it?' A formal assessment (with appropriate actions taken) will enable one to defend a position against the 'permit effective cleaning' standard.

10.2 No - This does not mean you must have automated detection equipment. It says 'a validated system' which could alternatively mean a 'validated' manual system of, for example, flagging and removal – the intention was to emphasise the importance of having a reliable system of removing this type of defective product.

return to top of page

Question (2003-03)

This is to confirm our telephone conversation and my request for the PQG to offer guidance in relation to paragraph 10.1.2 Verification methods / equipment and a non-conformance arising out of a pharmaceutical quality audit. The concern is in regard to the requirement under paragraph 10.1.2, Scanning of security barcodes, that ' The scanning equipment software/ control configuration shall be loaded from an independent source (e.g. specification or approved proof)'. In practice our production folder/gluing machines have no provision to manually enter a code sequence. It is necessary to feed a carton, carrying the security gluer barcode, under the scanning head for the barcode to be recognised and 'entered'. Our documentation provides controls including a barcode assignment register and traceability to a specification and approved proof, demonstrating that a unique bar code has been used. We understand that this method is standard practice in the carton industry. Can the PQG consider the issue and comment as to whether the process in use satisfies the requirement, or offer guidance to that end.

Answer

Scanning, as part of a well thought out procedure, can ensure that the components all have the same code, but also that the correct code (versus the job documentation) is being used. The reason for setting the bar code scanner from an independent source is to reduce the risk of processing the incorrect job. If the scanner is set simply using a carton from the job itself then this misses the opportunity to ensure that the work-in-progress actually matches the job documentation. When there is no facility to manually enter a code, then scanning a code from an approved specification / proof is considered acceptable. It is important that the carton used to program the scanner has been verified by an independent check to have the correct code for the work-in-progress and for the documentation set.

return to top of page

Question (2003-02)

To comply with clause 9.1.1 of PS 9000 our company is required to use coated or covered lighting "where product is exposed". The statement in PS 9000 does not allow for an assessment of statistical risk and as a consequence, organisations may find themselves facing a potentially large financial outlay for the elimination of a risk that, in some cases, has an extremely low probability (i.e. probability of occurrence X probability of contamination). Is a risk assessment appropriate in such cases? What constitutes an "exposed" product?

Answer

This is an important question which auditors find results in lively debate. The reason that PS 9000 contains this requirement is to prevent small fragments of glass that could occur as a result of breakage, from becoming attached to printed materials. It is important that this potential defect is avoided to maintain patient confidence and to avoid the justifiable complaint that could result. A good way to look at this situation would be to ask oneself the question: "What would my reaction be if I discovered a very small fragment of glass inside a pack of medicines or attached to an information leaflet?" We believe that no one would find this acceptable. Consequently the PQG sees no place for a statistical approach to deciding whether protected lighting should be used because the objective is to achieve zero defects for this type of defect. However, a form of risk assessment is required in that the manufacturing company should decide objectively where the printed materials (product) are exposed. Exposed in this sense means that product is not packed in protective packaging, or protected by the machine itself so that foreign matter (including glass particles) can fall on it and contaminate the product. This targeted approach should result in control where it is necessary whilst minimising cost. As a guide, areas where protection is considered essential are the presses (unless the press itself provides the necessary cover), guillotine, breaking-out, cut & crease, gluing and packaging areas. Other areas that may require protection are: i) the pre-press area, if product is exposed ii) UV tubes in UV presses iii) viewing tables and/or cabinets iv) UV light type insect killers if they are sited in risk areas. Note: it is not essential to protect lights in areas where product is covered or otherwise protected, e.g. storage areas, "Work in Progress" areas, corridors, origination and plate making areas, however an appropriate risk assessment should be carried out in those areas to confirm that such protection exists.

return to top of page

Question (2003-01)

We are interested in PS9100-2002 and would like to know, which companies are already certified for PS9100-2002, and also which certifying bodies in Germany are able to certify PS9100-2002.

Answer

PS9100 is a comparatively new standard and no companies are currently certified to it although some are certified to its predecessor (P00020). A list of certified suppliers to the PS series is maintained on the Pharmaceutical Quality group web site (www.pqg.org) in the PS9000 section. The certification bodies that certify to the standards are listed in the Frequently asked questions section, but these are only UK companies at present. Whilst the Certification Bodies listed on the PQG website are undertaking audits to the IQA/PQG Codes of Practice, PS 9000 and PS 9100 in the UK and Ireland, none have been carried out to date in other European countries (or at least none have been recognised by the PQG as meeting the requirements of PS 9000 Annex E or PS 9100 Annex B). However, a number of organisations, in other European countries, supplying to the pharmaceutical industry are working to PS 9000 Pharmaceutical Packaging Materials and PS 9100 Pharmaceutical Excipients and their precursor Codes of Practice (P00020 - Raw Materials, P00021 Printed Components and P00022 Contact Packaging Materials). Two other organisations in Europe have developed similar standards and related certification schemes over the last decade, viz. Certipharm in France and QAPP in Germany. I, representing the PQG, am in dialogue with Certipharm and QAPP with a view to each organisation recognising each others standards and certifications initially and then proceeding to harmonisation of standards, auditor training, auditor registration and certificates. According to the International Accredited Certification rules and ISO 19011, audits (including auditors) shall 'take account of the language of the organisation'. If audits were carried out from the UK, using the current registered auditors, a suitably qualified translator would be required. Both Certipharm and QAPP may be able to offer you Certification to PS 9100 in Germany (using a German speaking auditor) supported by a PS 9000 (9100) auditor in accordance with the requirements in PS 9100 Annex B. Currently, there are no German or French speaking auditors recognised although I anticipate this will change in the foreseeable future as PS 9000 and PS 9100 become more widely recognised and additional auditors are trained and certified. Certipharm and QAPP are seeking companies to work with to pursue their European Certification objectives and are able to certify to PS 9000 and PS 9100. Also under discussion is a plan to translate PS 9000 and PS 9100 into French and German.

return to top of page

Question (2002-06)

Can you tell me whether P00021, the predecessor to PS9000 is still valid?

Answer

Yes the Codes of Practice are still valid until December 2003 after which PS 9000 becomes the appropriate standard. There is of course no reason why the company could not align itself with PS 9000 earlier than this date and we would recommend this is done.

return to top of page

Question (2002-05)

I've tried finding information on training courses for auditing to this standard and have not found any to date. Can you let me know or pass on my query regarding this to the relevant person?

Answer

Training courses are provided by the 3 course providers - click here for their details:

return to top of page

Question (2002-04)

We wish to become certified to PS9000, but are unsure, which certification bodies are currently approved. There seems to be little information on the larger Certification Bodies' websites and although the PQG site gives names of auditors, I cannot see the names of any companies.

Answer

The following seven Certification Bodies (as published on the PQG website) have committed themselves to the Codes of Practice/PS 9000.

• AJA Registrars
• BSI Management Systems
• Bureau Veritas Quality International
• Det Norske Veritas
• National Standards Authority of Ireland
• National Quality Assurance
• SGS Yarsley International Certification Services

These Certification Bodies (and other Accredited Certification Bodies) should be able to undertake Code of Practice/PS 9000/PS 9100 assessments in accordance with Annex E of PS 9000 and Annex B of PS 9100 using suitably qualified auditors.

return to top of page

Question (2002-3)

We have just recently been audited by BSI (surveillance audit + transition to ISO9001: 2000 & PS9000: 2001) & have a query/concern about what is quoted in Annex E, section 1.1 (d).

This part says that we are obligated to supply any audits performed by BSI to customers if requested. This is a conflict of interest as the information viewed by BSI is strictly confidential. We have a large number of customers & we do not believe it is in anyone's interests for customers to view any information that does not pertain to them.

Answer

The PQG request audit reports to be available in order to monitor suppliers from time to time to recognise their certification, as the Certificate alone does not provide sufficient information.

Customers and potential customers should have access to 3rd party Certification reports (which normally do not contain confidential information only audit deficiencies) prior to and after placing orders. Knowledge obtained can assist in selection of a supplier and also reduce the pharmaceutical customer audit frequency and content (both prior to purchase and subsequently). However, if there are particular confidentiality issues in a report related to another customer then this could be omitted from the copy.

Access to the reports does not necessarily mean that copies have to be given to the customer. Often, a sight of the report will be sufficient for the auditor / Customer.

return to top of page

Question (2002-02)

Is there a list of UK Pharmaceutical Auditors?

Answer

The PQG website contains the list of IRCA registered QMS & PS 9000 Auditors

return to top of page

Question (2002-01)

Query on PS 9000: 9001 Packaging materials following feedback from auditor training course. PS 9000: 9001 is less demanding than original COP with respect to control of change at the supplier.

Answer

Section 7.2.3 Customer Communication

The referral is that paragraph 3 is less demanding than the equivalent section of the last COP, where it affects the technical dossier. The background to our PS 9000, so that we split the issue of communication on control of change at the supplier into two areas:

1. Changes requiring documented approval. This we believe was a comprehensive catch all paragraph as it includes changes to;
   1. Product specification
   2. Customer specified starting or raw materials
   3. Process changes
   4. Test methods etc

It was believed that these were essential and 'reasonable'

2. Changes requiring notification. These we believed brought to the customers attention all other possible changes which are of importance to the customer. They include:
   1. Change of site, facilities, equipment
   2. Change in the quality/corporate organisation
   3. Dossier changes

It was considered that a and b are examples of direct corporate responsibility, not requiring customer approval and to 'try' to demand otherwise is unreasonable (and not likely to succeed).

The example of the dossier change(c) must be related to Section 7.3.2 Design and Development inputs, where to "facilitate supplier confidentiality scientific and technical information may be supplied directly as a dossier to the regulatory authorities for example in the form of a Drug Master File (DMF)".

It is in this context that notification of changes was written.

There are a couple of other points all in PS 9000

1. Any changes to process, product, test material etc do require approval, (as already detailed in the above)
2. Key changes allows for "customer performing a stability and compatibility retesting programme.... which may take up to 12 months or more...for approval"
3. "Changes that affect any of the data supplied by the by the organisation shall be communicated to the customer or the regulatory authority" (i.e. in the context of confidentiality of the DMF).

These sections were written in full awareness of the reality of commercial supply where customers can be kept in the dark until too late. Also that suppliers themselves occasionally lose their source of supply and have to find alternatives which are often presented to the all those in the customer chain as 'take it or leave it'

The important issue we judged was to be realistic and pragmatic, with clarity over the key 'approval' requirements.

This query was in two parts.

The sub-part referred to "what is meant by 'a dossier', I think I've outlined that there is adequate information in the text, specifically Section 7.3.2.

If you can review this second set of referrals and let me have your comments, then I can get back to the Partners Team with our definitive response (i.e. as an ongoing up-date to PS 9000 in the market place.

The medium term expectation is that all these referrals and responses will go onto the PQG website so that all organisations have visibility of feedback and qualifications.

return to top of page

Question (2001-02)

Query on PS 9000: 9001 Packaging materials following feedback from auditor training course. Please can you give further guidance on the Environmental Control requirements, as covered by section 9.2.

Answer

9.2.1 Minimum environmental conditions These conditions are appropriate for the processing of secondary materials, for example cartons and labels. They are also suitable for product contact materials where no higher environmental conditions are specified by the customer, for example;

1. tablet blister film
2. injection moulded plastic tablet containers and closures

9.2.2 Standard cleanroom conditions These conditions are in addition to the requirements of PS 9000 9.2.1, for minimum environmental conditions. They are appropriate for the processing of product contact packaging materials where there is a customer requirement for 'clean' materials produced under conditions that control particulate contamination and where the customer may carry out further cleaning treatment, for example;

1. glass vials supplied to a customer prior to further processing, which could include washing and sterilising, prior to the filling process.
2. metered dose valves
3. closures and ancillary components for parenteral or ophthalmic containers

9.2.3 Enhanced cleanroom conditions These conditions are in addition to the requirements of PS 9000 9.2.2, for standard cleanroom conditions. They are appropriate for the processing of product contact packaging materials where there is a customer requirement for control of bioburden and when there is a later material sterilisation process either pre or post delivery to the customer, for example assembly of syringe components for subsequent sterilisation.

return to top of page

Question (2001-1)

Is it possible for a supplier to maintain certification to 'PS 9000 : Pharmaceutical packaging materials' even though a customer of the supplier formally asks or instructs that supplier to employ composite gang printing?

Answer

Background Clause 13.5 of PS 9000 does not permit gang printing. There is no statement on this subject in the EU GMPs although European Medicines Inspectors are strongly against this practice. The US CFRs make a clear statement in 211.122 (f) i.e.

'Use of gang-printed labeling for different drug products or different strengths or net contents of the same drug product, is prohibited unless the labeling from gang printed sheets is adequately differentiated by size, shape or color.'

PQG Response This question was discussed at the Steering Group meeting on 28 March 2002 and the response agreed is:

1. The Steering Group strongly believes that the use of gang printing introduces a serious risk to patient safety through admixture that should be avoided. It further believes that pharmaceutical customers should not request their suppliers to use gang printing for their materials, as this is not consistent with accepted best practice. It does not intend to alter Clause 13.5 of PS 9000.
2. The content of the contract in place between a supplier and its customers is not PQG's business. This means that if a customer insists on asking a supplier to employ gang printing the PQG cannot intervene.
3. However, we can envisage a process whereby a supplier can meet this customer requirement and maintain its certification to PS 9000. That process is:
   1. The supplier must state in their Quality Manual, as required by clause 4.2.2, the conditions under which it does not comply with clause 13. This statement should encompass how items
   2. - iv) are managed.
   3. The supplier must confirm in writing to their customer that product has been produced outside the scope of PS 9000 in respect of clause 13.5. This could be on the certificate supplied with each batch, in the contract, or by letter.
   4. We strongly recommend that the supplier seeks an understanding from the customer that if any gang printed items are to used for the US market that the printed sheet complies with CFR 211.122(f). We also recommend that this is recorded, subject to change control and also defined in the contract.
   5. Even where product is not destined for the USA, we also recommend that the supplier seeks to agree with the customer compliance with CFR 211.122(f).