bromi variations training meeting 8th may 2008 case study session bromi variations

BROMI Variations Training Meeting 8th May 2008

Case Study Session

BROMI VARIATIONS.


PLAN

• How this session will work.– A presented example (Case Study 1) to give

you an idea of what you should be looking for.– Then there will be up to 3 further case studies

for you to work through:• More complex than first example.• Time for discussions – answer questions.• Try to work out how you would do it.• BROMI or not and highlighting potential issues.


PLAN• ‘Model’ answers to all four case studies

will be provided in the delegate pack to allow you to train others.

• Set-up for round-table discussions.• Please nominate a table leader to

feedback answers to questions during this session.

• Any questions please ask the industry or MHRA support on hand.


CASE STUDY 1.


PROBLEM.

• Company A sells pain reliever tablets

• Section 6.5 of the SPC describes the current packaging as:– Blister strips consisting of a base layer of 250

micron PVC with lidding foil of 20 micron aluminium foil, in packs of 8 or 16 tablets

• The company wishes to add a pack size of 12 tablets.


QUESTIONS.• Could this be a BROMI change, if so which one?• What conditions are there for the change and do

we meet them?• What documentation would be required?• Do we have sufficient information available to

submit this application as a BROMI change? If not what additional data would we need to provide?

• Is there anything additional we would submit?


ANSWERS.• Could this be a BROMI change, if so which

one?– Yes, before the BROMI variations this would have

been a Type IA now it could be a BROMI Self Certification category 41.a.1


ANSWERS.• What conditions are there for the change and

do we meet them?


ANSWERS.• What documentation would be required?

– Cover Letter– Completed Portal Application Form.– Completed BROMI variations guideline page– Proof of Payment (according to company procedures)

• PLUS


APPLICATION FORM.


BROMI GUIDELINE PAGE.


ANSWERS.• Do we have sufficient information available

to submit this application as a BROMI change? If not what additional data would we need to provide?– Yes. As the required pack size is within the current

range this can be submitted as a BROMI Self certification. No stability declaration is required.

• Is there anything additional we would submit?– No


DISCUSSION / QUESTIONS

• Any questions on first case study example?


CASE STUDY 2.


PROBLEM• Company A sells Pain Reliever Tablets.• Section 6.5 of the SmPC describes the current packaging as:

– Blister strips consisting of a base layer of 250 micron PVC with lidding foil of 20 micron aluminium foil containing 8 tablets, in pack sizes of 8 or 16 tablets.

• The company wishes to change the lidding foil to a thicker material which consists of 20 micron aluminium foil and 15 micron PVC. – A specification for the new packaging material is available. – The company has also done some work to compare the permeability of

the new packaging with the old packaging to show that the product does not interact with either PVC or Aluminium foil.

– Stability studies with the new packaging have been started this week


QUESTIONS• Could this be a BROMI change, if so which

one?• What conditions are there for the change and

do we meet them?• What documentation would be required?• Do we have sufficient information available

to submit this application as a BROMI change? Is there anything additional we would submit?

• Fill in blank Portal Application form (pertinent sections only)


ANSWERS

• Could this change be a BROMI change, and if so which one?– Yes, it could be a BROMI Type IB change,

code no. 29.c : – ‘Change in the qualitative and/or quantitative

composition of the immediate packaging material - All other pharmaceutical forms – change concerns more resistant packaging and stability data are not yet available’


ANSWERS

• What conditions are there for the change and do we meet them?– The product concerned is not a biological or sterile product.– The change only concerns the same packaging type and

material (e.g. blister to blister).– The proposed packaging material must be at least equivalent to

the approved material in respect of its relevant properties.– The proposed packaging is more resistant than the existing

packaging e.g. thicker blister packaging and three months’ stability data are not yet at the disposal of the applicant. Assurance is given that these studies will be initiated and finalised and that the data will be provided immediately to the competent authorities if outside specifications or potentially outside specifications at the end of the approved shelf life (with proposed action).


ANSWERS• What documentation would be required?

– Cover Letter– Completed Portal Application Form– Completed BROMI variations guideline page (checklist)– Proof of payment (according to company procedure)– Revised dossier pages (Module 3.2.P.7).– Justification for the omission of stability data and stability

commitments. In module 3 or as a separate statement)– Comparative permeability data.– Discussion of the original interaction data and it’s relevance to

the new packaging.– Revised SmPC section 6.5– Present and Proposed Specification


ANSWERS

• Do we have sufficient information available to submit this application as a BROMI change?– Yes, sufficient information is available.


CASE STUDY 3.


PROBLEM• Overview of the proposed changes to be

made:– Change in the name and address of the MA

holder– Change in the name of the manufacturing site– Addition of a new pack size

• Impacted Licences– ParaTabs Children’s Tablets– ParaTabs Adult’s Tablets


PROBLEMChange 1 - Change the name and address of the MA holder from :

ABC Pharmaceuticals1 High StreetPharmatownUKCompany number: 1234

to

XYZ Pharmaceuticals1 The Business ParkPharmatownUKCompany number: 1234


PROBLEMChange 2 - Change the name of the manufacturing site from:

ABC PharmaceuticalsPharmaplantParisFrance

to

XYZ PharmaceuticalsPharmaplantParisFrance


PROBLEM

Change 3 - Addition of a new pack size

– New pack size: 4 tablets for each licence– Current pack sizes on licence: 2 & 6 tablets– Packaging material remains the same


QUESTIONS• Can these changes be submitted as BROMI

applications? • What conditions are there for each change and do

we meet them all?• What documentation would be required?• Do we have sufficient information available to

submit these applications as BROMI changes? If not what additional data would we need to provide?

• What strategy would you use?• Fill in blank Portal Application form (pertinent

sections only)


ANSWERS.CHANGE 1: • Could this be a BROMI change, if so which

one?– Yes as Company remains the same legal entity– Self certification BROMI No. 1: Change in the name

and/or address of the marketing authorisation holder.• What conditions are there for the change and

do we meet them?– MA holder must remain the same legal entity– The changes are the only changes to be made, other

than those stated which are being submitted in parallel.


ANSWERS.CHANGE 1(Cont):• What documentation would be required?

– Cover Letter– Completed Portal Application Form– Completed BROMI variations guideline page (checklist)– Proof of payment (according to company procedure)– Companies House Certificate– Proposed SPC (and fragment) and artwork (as appropriate)

– in this case: carton, foil and joint PIL for each product• Do we have sufficient information available to

submit this application as a BROMI change? – Yes.

• Is there anything additional we would submit?– No.


ANSWERS.

CHANGE 2: • Could this be a BROMI change, if so which one?

– Yes as this remains the same company submit under:– Self certification BROMI No 5: Change in the name and/or

address of a manufacturer of the finished product.

• What conditions are there for the change and do we meet them?– Manufacturing site remains the same– The change is the only change to be made, other than those

stated which are being submitted in parallel.


ANSWERS.CHANGE 2 (Cont):• What documentation would be required?

– Cover Letter– Completed Portal Application Form– Completed BROMI variations guideline page (checklist)– Proof of payment (according to company procedure)– Formal document with new name (in this case a GMP certificate)– Updated CTD pages– Updated artwork as appropriate

• Do we have sufficient information available to submit this application as a BROMI change? – Yes.



ANSWERS.CHANGE 3: • Could this be a BROMI change, if so which one?

– Yes, the new pack size to be added is within the current range so can be submitted as:

– Self certification BROMI No. 41, a 1: Change in pack size of finished product within the currently approved range (By referencing the SPC you can see that 2 tablet and 6 tablet pack sizes are currently registered).

• What conditions are there for the change and do we meet them?– The new pack size is consistent with the posology – Primary packaging remains the same– The smallest and largest pack sizes remain on the licence– The change is the only change to be made, other than those

stated which are being submitted in parallel.


ANSWERS.CHANGE 3 (Cont): • What documentation would be required?

– Cover Letter– Completed Portal Application Form– Completed BROMI variations guideline page (checklist)– Proof of payment (according to company procedure)– Proposed SPC (and fragment)– Proposed carton, foil & leaflet for each product– Updated CTD pages– Stability data is not required as the stability parameters are not

affected.• Do we have sufficient information available to submit this

application as a BROMI change? – Yes.



ANSWERS.

CHANGE 3 (Cont):

• STRATEGY:– The 3 changes can be submitted in parallel


CASE STUDY 4.


PROBLEM

• Company A sells pain reliever tablets• It would like to use paracetamol manufactured by Active

P Supplier Inc in their tablets. This is a new supplier.• Active P Supplier Inc has a European Pharmacopoeia

Certificate of Suitability (CEP) for paracetamol.• It has a number of suppliers of paracetamol on its

licences, however it would also like to remove Paracetasupply Ltd from the licence.

• Paracetasupply Ltd is listed as an API (Active Pharmaceutical Ingredient) manufacturer on three other of company A’s licences.


QUESTIONS• Could the above changes be handled as BROMI

changes, if so which one(s)?• What conditions are there for the changes and do we

meet them?• What documentation would be required?• Do we have sufficient information available to

submit relevant applications? • If not what additional data would we need to

provide?• What is the most efficient way of removing

Paracetasupply Ltd from all three licences?• Fill in blank Portal Application form (pertinent

sections only)


ANSWERS• Could this be a BROMI change, if so which

one?– The addition of a new CEP could be submitted as

a BROMI Self Certification change code 15 a 2 if the manufacturer is currently approved (Updated CEP) but in this case the manufacturer is not currently approved and so the variation should be submitted via the standard Type I A route, change code 15 b 2.

– The deletion of Paracetasupply Ltd on the 3 licences can be done as a BROMI change code 9a.


ANSWERS• What conditions for the changes and do we meet them?

Type I A Code 15 b – The finished product release and end of shelf life specifications remain the

same.– The finished product release and end of shelf life specifications remain the

same.– The active substance will be tested immediately prior to use if no retest

period is included in the European Pharmacopoeia certificate of suitability or if data to support a retest period is not provided.

– The manufacturing process of the active substance, starting material/reagent/intermediate does not include the use of materials of human or animal origin for which an assessment of viral safety data is required.

BROMI Change code 9a– An appropriately authorised site remains registered on the authorisation to

undertake the manufacturing operation concerned.


ANSWERS• What documentation would be required?Type I A Code 15 b

– Copy of the current (updated) European Pharmacopoeia certificate of suitability. – Amended page(s) of Part IIC and IIF (old Part IIE) or equivalent in the CTD

format, if applicable– Where applicable, a document providing information of any materials falling

within the scope of the Note for Guidance on Minimising the Risk of Transmitting Animal Spongiform Encephalopathy Agents via Human and Veterinary Medicinal Products including those which are used in the manufacture of the active substance. The variation application form should clearly outline the “present” and “proposed” manufacturers as listed in section 2.5 of the (Part IA) application form.

– A declaration by the Qualified Person (QP) of each of the manufacturing authorisation holders listed in the application where the active substance is used as a starting material and a declaration by the Qualified Person (QP) of each of the manufacturing authorisation holders listed in the application as responsible for batch release. Cover Letter

– Proof of payment (according to company procedure)– Completed application form– Completed variations guideline page (checklist)– Cover Letter


ANSWERS• What documentation would be required?

BROMI Change code 9a– Cover letter– Completed BROMI variations guideline page

(checklist)– Completed Portal Application Form– Proof of payment (according to company procedure)– The “present” and “proposed” manufacturers should

be clearly stated on the variation application form.– Updated Module 3 pages in CTD format


ANSWERS

• Do we have sufficient information available to submit this application as a BROMI change? If not what additional data would we need to provide?– No, for the addition of the API supplier. We have the current

European Pharmacopoeia certificate of suitability but we require a signed QP declaration before submission.

– Yes to remove the API manufacturer, Paracetasupply Ltd . The licences still include an API supplier Paracetamol Supplies Ltd.

• Is there anything additional we would submit?– No


ANSWERS

• What is the most efficient way of removing Paracetasupply Ltd from all three licences?– As with standard, non-BROMI variations bulk

applications are acceptable.

bromi variations training meeting 8th may 2008 case study session bromi variations

Documents

bromi change

bromi type ib change

bromi guideline page

available slide

week slide

current packaging

packaging type

micron aluminium foil