1. Does the MHRA inspect compounding (eg hospital preparation or registered pharmacy units) not holding Manufacturer’s/Importer’s Licences (MIAs)? If so, to what standards?
2. How can companies get involved in legislation consultation processes?
3. Please clarify: there should be a technical agreement between the MIA holder and the QC site responsible for testing. Does this QC site also need to be listed on the marketing authorisation?
4. What is the MHRA’s view on information from questionnaires?
5. Could a company have a risk based approach on a new vendor?
6. How does the MHRA check QPs are familiar with a company’s quality management system before approving them on a variation?
7. What stability considerations are required if a change is made to a product contact part of a parenteral product eg tubing?
8. What are the timelines for implementation of a non-safety change to a pack?
9. How often are unannounced inspections performed and will risk based inspections increase this?
10. Is any consideration given to the number of sites a QP is named against, not just the number of licences?
11. Under what circumstances may it be considered feasible to destroy paper originals of GMP documents?
12. What are the rules for over-labelling by a community pharmacist?
1. Does the MHRA inspect compounding (eg hospital preparation or registered pharmacy units) not holding Manufacturer’s/Importer’s Licences (MIAs)? If so, to what standards?
Many compounding units are exempt from inspection by the MHRA because they operate under Section 10 of the Medicines Act ie under the supervision of a pharmacist. Units holding a Specials Licence (MS) where products are manufactured that do not hold marketing authorisations, are inspected to the same GMP standards as MIA licensed premises.
2. How can companies get involved in legislation consultation processes?
There is a distribution network for legislation to key stakeholders, however there is also a public consultation process which companies and individuals can get involved in. Announcements for future consultations and results of past ones are published on the European Medicines Agency (EMA) and European Commission (EC) websites. The MHRA also issue consultation papers, individuals can subscribe to be notified of these through the MHRA website.
3. Please clarify: there should be a technical agreement between the MIA holder and the QC site responsible for testing. Does this QC site also need to be listed on the Marketing Authorisation?
Yes, this is correct and establishes all sites in the chain. The site will also be named on any manufacturing authorisations (MA) for which the testing is being undertaken.
4. What is the MHRA’s view on information from questionnaires?
Questionnaires should not be stand alone documents but should be built into a company’s supplier approval process. Questionnaires should cover GMP aspects. Companies also need to consider how the information returned is assessed and by whom, and how any decisions on the suitability of a supplier are recorded. Suppliers should not be accepted on the basis of a questionnaire alone.
5. Could a company have a risk based approach on a new vendor?
Every decision re the choice of a new vendor will involve a risk assessment. We would expect this to be part of the vendor selection and approval process.
6. How does the MHRA check Qualified Persons (QPs) are familiar with a company’s quality management system before approving them on a variation?
A QP has a professional duty to be familiar with a company’s quality system. The responsibility of the MHRA is to assess the QPs suitability to be named on a particular authorisation. This will involve considering their qualifications, experience, work load and past history as well as assessing whether the proposed time allocation to the site is adequate to maintain a familiarity with, and influence over, the company’s quality system.
7. What stability considerations are required if a change is made to a product contact part of a parenteral product eg tubing?
This would need to be considered on a case by case basis with a pharmaceutical assessor and follow the appropriate variation process. However, in general a change control and a risk assessment would be required, as would compatibility studies. Stability studies would not necessarily be required before use, but samples should be set down on the first batches manufactured.
8. What are the timelines for implementation of a non-safety change to a pack?
Generally three-six months is accepted for a non-safety change to a pack. Safety changes have a tighter timeline. If a company cannot meet these dates, then the MHRA should be informed.
9. How often are unannounced inspections performed and will risk based inspections increase this?
We do not monitor the number of unannounced inspections performed. Unannounced and short notice inspections are a useful tool and are normally triggered by information received within the inspectorate. The Risk Based Inspection programme may provide opportunities to improve the data gathering or intelligence known about an operation and this in turn may increase the number of triggered inspections of this type.
10. Is any consideration given to the number of sites a QP is named against, not just the number of licences?
Although different sites on the same licence generally have the same quality management system there is still a concern as the number of sites increase. There is no maximum number set, although further information will be requested if the number of sites a QP is named on seems high.
11. Under what circumstances may it be considered feasible to destroy paper originals of GMP documents?
Companies are advised to perform a risk assessment before destroying any essential or source documents. Such documents may be transferred into an electronic format, with the originals being destroyed provided:
- the mechanism of transfer is appropriately validated and this has been documented
- written procedures exist to describe the process for transfer and the arrangements for long-term retention
- adequate Quality Control (QC) checks are performed and documented during the transfer process (to provide assurance that unacceptable errors have not occurred during the transfer process)
- electronic media are appropriately stored for long-term retention (with acceptable back-ups, where appropriate)
- periodic QC checks of the electronic copies are performed, where appropriate (to check for degradation, for example for microfiche)
- a risk assessment is performed and documented by the company with respect to the destruction of original copies, for example if litigation is an issue, then it may be inappropriate for the company to destroy original records relating to the development or use of this product
12. What are the rules for over-labelling by a community pharmacist?
1. Section 10(1) of the Medicines Act 1968, as amended, provides a pharmacist or any person working under their supervision in a registered pharmacy, hospital, a care home service or health centre, with an exemption from the requirement to hold a manufacturer's licence to:
a) prepare or dispense a medicinal product in accordance with a prescription given by a practitioner, or
b) assemble a medicinal product. If the assembly takes place in a registered pharmacy. The assembled product is for retail supply or circumstances corresponding to retail supply. The assembled product must be sold from that pharmacy or at any other registered pharmacy forming part of the same retail pharmacy business. The assembled product cannot be advertised.
Section 10(1)(a) and 10(1)(b) are separate activities.
2. Hospitals use the section 10 exemption to prepare stock for use within their own legal entity.
3. The labelling requirements for dispensed medicines are contained in Schedule 5 of The Medicines for Human Use (marketing authorisations etc) Regulations 1994 [SI 1994/3144] as amended.
4. Outside the conditions of 1. above, an over label may only be applied to a licensed original pack by the holder of a full or assembly only manufacturer's licence (not a manufacturer's 'specials' licence) , but please note that:
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the over label must not obscure the printed text of a licensed pack in any way
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the over label should be applied to the blank area designated on the original pack for the dispensing label
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in cases where an original pack does not have provision for a dispensing label, the over label should be firmly attached to the pack in a manner that is easily readable and does not obscure the licensed text nor interfere with the safe and effective use of the medicine
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original packs over labelled in accordance with these principles may be supplied direct to hospital pharmacies, health centres etc without the necessity for formal variation of the marketing authorisation by the marketing authorisation holder.
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breaking bulk (manufacturer's original pack) will require a variation to the respective marketing authorisation.
5. Pharmacists operating under section 10 of the Act are controlled by the Royal Pharmaceutical Society of Great Britain (RPSGB).
