Feedback for Seeking Feedback on Non-Sterile Compounding Standards

Pharmacist  ·  Nov. 18, 2016

I have a number of comments and questions regarding the NAPRA Model Standards for Pharmacy Compounding of Non-Sterile Preparations. Overall, this is a very good document (but not an easy read ). From the limited comments I read on your website, I don’t think some members understand the implications of these guidelines and that they will have to meet them no matter what amount of compounding they do.

Next, you unfortunately did not give members adequate time to read this large document and make comments. You sent this out on October 20, 2016 and have given us a deadline of November 17, 2016. This is not enough time to get back adequate and meaningful dialogue from your members. I am very upset about this short time-line as are others who would have given feedback but did not have the time. I had to spend a lot of my time in the evenings to do this.

Under Regulatory Framework – says the compounding must always be carried out within a prescriber-patient-pharmacist relationship … and that Health Canada (HC) was examining policy 0051 with a view to creating new standards for situations not covered within the practice of pharmacy or under the current federal licensing framework, such as ‘commercial compounding manufacturing’. Please define ‘commercial compounding manufacturing’ as these have opposite definitions. Appendix 1 where it shows the differences between compounding and manufacturing – we need clarification from OCP and HC regarding third party compounding pharmacies that make large batches of compounds, then sell to pharmacies in Ontario or other provinces. Is this compounding or manufacturing? According to the current 2009 version of policy 0051 this activity is more manufacturing than compounding. If our pharmacy contracts out and buys products from such a compounding pharmacy, does this not break the prescriber-patient-pharmacist relationship as we have bought from a 3rd party?? Does OCP allow this? What if the compounding pharmacy is from another province? What are the legalities? So if you look at Appendix 1 –Q1 about patient-healthcare relationship – wrt the compounded product – this would be ‘No’ as the 3rd party has no relationship, just the pharmacy who bought the compounded product. For Q2 – third part reselling of the product outside the relationship – answer is yes and Q5 about inordinate amounts of product produced on a regular basis the answer is Yes again as the compounding pharmacy is selling to many pharmacies. Therefore, as it stands, I interpret 3rd party compounding and selling to be more manufacturing. I hope this is what HC is redefining in Policy 0051, but we also need a clear statement from OCP on what all Ontario pharmacies are allowed to do as many are buying from these compounding centers now. Furthermore, as it stands now, HC policy 0051 states ‘in circumstances where an individual cannot clearly determine whether a particular activity is considered to be manufacturing or compounding, they may either contact the Health Products and Food Branch Inspectorate or the respective provincial/territorial regulatory body. At that point, discussions may take place between the two jurisdictions for final determination of whether an activity is considered to be compounding or manufacturing. In situations where the provincial/territorial regulatory authority decides that an activity does not fall within its jurisdiction, the activity is likely to be manufacturing’. I am very interested on getting an answer from OCP very soon.

-p 11 on non-sterile compounded preps made with approved ingredients … DIN or API used in a product approved for ‘Human or veterinary’ in Canada – I think you need to define Human or vet use otherwise pharmacists may use chemicals not approved for human use. However, if you do this, then this does not allow pharmacists to compounding from non-pharmaceutical chemicals (ie p 27 where they are allowed to choose ACS grade which would not have the necessary heavy metal or solvent testing required). However, I think this needs to be given more thought by NAPRA. I personally would never use an ACS grade. Just because it is high quality, this is designed for lab purposes only, not designated for human use (and can state that on the bottle) and it will not meet compendial testing. The chemical may contain high amounts of impurities or solvents that could be harmful. -what about the use of NPH products for compounding – this isn’t mentioned anywhere?

-The level – descriptions on pages 13, for requirements for Level B –well ventilated room and if hazardous products are being used the room must also be ventilated to the outside OR have a ventilated containment device- does not match p 38 where it describes room must be entirely closed off OR a room with a ventilated containment device is required with the air exhausted to the outside which does not match Appendix 21 where it just says Level B is a separate room well ventilated OR with ventilated hood (does not say vented to outside). This is not consistent throughout this document and has confused a lot of people. This must be updated to say the EXACT same thing on all 3 sites. This also goes for Level C – says on p 13 ‘room under negative pressure, a ventilated containment device’, p 40 says Level C requires compounding in a closed-off room under negative pressure with filtered air exhausted to the outside and Appendix 1 says separate room under negative pressure only. Again, needs to consistently say the same requirements throughout the document. Please fix this.

-p 16 mentions mandatory and supplementary references, but appendix 7 only says supervisor is to make available the required references, standards, guidelines and policies of the relevant pharmacy regulatory body. So I interpret this as the only mandatory reference. Is this the intent? -p17 – last paragraph I find confusing – need to determine who is responsible for which aspects of patient care if a product was prepared on behalf of another facility/pharmacy????? Both parties are responsible for that compounded product and would it be the pharmacist who dispenses it have the most responsibility to the patient (counselling etc). I am confused by this statement and don’t follow what they are trying to convey. -p20-‘appropriate temperatures and humidity monitoring should be maintained – what is the ‘appropriate’ humidity ranges then? RT has a definition – included in appendix 11, but no humidity is defined. -p23- packaging and cardboard boxes from products used must be removed from the non-sterile compounding area – this is extremely difficult to do in some pharmacies as items in boxes need to then be stored on shelves which there may not be an adequate number. It think it is realistic to re-word this and state ‘all packaging and cardboard boxes from products must be removed once drug is taken out of these boxes. Cardboard boxes should be kept to a minimum in the compounding area’- or something like that. -p24 says that compounded drug preparations are to be packaged in 'air-tight' light-resistant containers. No plastic bottle is airtight, only glass is. Since many drugs are dispensed in plastic bottles in pharmacies then it would be better described to be packaged in 'appropriate light-resistant containers'. -p 25 Master formulation record: ‘compatibility and stability data including references when available; source or origin of the formula; references used to write the formula and consultation date are really the same thing. If you get a recipe from another center (consultation), then you must also get the reference- even if they use USP or experience – then it shows you it is not based on scientific data. For the changes made in the formulation sheet the supervisor must describe the change and provide rationale and references. How can this all go on a master formulation record (i.e. worksheet) as there may not be space? As long as it is documented in a product review or product file and then the new reference can be listed on the master formulation record (which is the worksheet). -Statement that ‘the development of a new master formulation must be based on scientific data and appropriate references must be documented’ – but what about existing formulations? They also need a review and have stability data associated with them, not just ‘new’ formulations. I would take out the word ‘new’. -p 27 – purified water – so pharmacies can no longer use distilled water?? -p 27 –previously mentioned – says can use FCC or ACS – but I think ACS acceptance needs to be reviewed again as Sigma will clearly state that they chemicals are not for human use. The statement these chemicals should be used cautiously – change to extreme caution as they are not approved for human use by the chemical company. If the ACS does not come from a GMP facility then this is a huge concern. -previously asked – use of NPH products for compounding? -p27 quality of ingredients – if product is not sourced from a recognized supplier and it is not of pharmaceutical grade (add this in to clarify further) then a qualified lab must analyze the product. So if you do keep under Sources of Ingredients that ACS can be used then the pharmacist must arrange this extra testing, correct? We need this to be 100% clear to Pharmacists that this must be done. -p27 compounders must not use any ingredients for compounding that have been recalled or withdrawn from the market – so is this for BOTH human and veterinarian purposes??? Need to be 100% clear on this. Also, there are exceptions to this like cisapride that HC will approve through SAP for human use. So you need to state these exceptions here, i.e. ‘only exception is it is approved through SAP by HC (and need to add if OK for vet use as well). Some chemical companies in Canada still might sell these banned drugs so pharmacies can still access them. Also, there is still the possibility of human ingestion (intentional or accidental) of this banned drug if dispensed for animals as it was still allowed to be compounded. This has to be clarified further please so all Pharmacists understand what they can/can't do. -p 28 Ingredients Log – leave up to pharmacy how to do this. This can be done without keeping a log – can have stickers for bottles with this information (a lot easier to do we find). -p 28 – Compounding record should contain– says it should have ‘Master formulation record reference for prep ‘– add –‘if not already using copy of this master record as the worksheet’. That’s what we do. -29 – rationale for compounding must be documented in the patients file… when there is a marketed drug available. This is easy for community, not for hospitals and they may not be able to comply as these drugs will be made in batches. -p29: do not wear jewelley on hands or wrists: Question: what if they use gowns and gloves that cover all their arms, wrists and hands so no skin or clothing is exposed. Since this is for oral compounding, in this situation can they leave rings on? -p29 ‘compounding personnel must ensure the prep is delivered to the patient or caregiver with appropriate consultation’ – can’t do this in a hospital. Please change wording to ‘compounding personnel or delegate’ that way the ward pharmacist or RN can do this. -p 31 – Label – pharmacy full address and phone number is NOT possible for hospitals. Our labels are small, go on oral syringes, small bottles and all necessary information will then NOT fit. Also, these are custom labels hospitals CANNOT afford and they may Not work with our automated machines. Please, please put an exemption after pharmacy identification please ‘exemption: hospital inpatients’. -p31 – Label – emergency contact information of the compounding pharmacy – this does not apply to hospitals and our inpatients. Please consider adding ‘exemption: hospital inpatients’ -P33 – again need humidity values -p36 8.2.2 – need to add in at end the Room environment temperature here as well, just not for freezers and fridges

I look forward to having more dialogue on these standards! Thanks again

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