COMPOUNDING PHARMACIES and its role in personalised medicine?

Personalised medicine also known as precision medicine is an innovative approach to disease prevention and treatment that takes into account differences in people’s genes, environments and lifestyles (U.S. FDA).

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Pharmaceutical compounding (CP) is both the art and science of the mixing of drugs by a compounding pharmacist to prepare personalised medications for patients, to meet the unique needs of a patient.  This may be done for medically necessary or valid reasons, such as to avoid adverse events, to change the form of the medication from a solid form such as a tablet to a liquid form for ease of administration or to avoid a non-essential ingredient that the patient is allergic to.

Compounded medications are “made from scratch” so to speak, where individual ingredients are mixed together in the exact strengths or doses required by the patient. This method allows the compounding pharmacist to work with both the patient and the prescriber, to customize a particular medication to meet the patient’s specific needs.

A compounding pharmacy is one in which pharmaceutical compounding occurs within a purpose-built laboratory, specifically for the purpose of making specialized preparations.

The progress in CP

Compounding was at one time the mainstay of pharmacy operations.  With the advent of mass drug manufacturing in the 1950s and ‘60s, pharmacy compounding gradually disappeared, and standard doses of drugs became the mainstay of drug treatment. However, this “one-size-fits-all” nature of many mass-produced medications meant that some patients’ needs were not being met while others experienced unwanted side effects or adverse events.

Compounding pharmacy operations have today experienced a resurgence, as modern technology coupled with innovative techniques and research, have allowed more pharmacists to customize medications to meet specific patient needs.  Consequently, trained pharmacists can now customize or personalize medicines for patients who have specific needs such as medication strengths, dosage forms for easier administration, flavouring especially for children, ingredients to exclude allergies, or medicines that have been discontinued by a manufacturer.  In essence, compounding pharmacies allow for more flexibility, options, and customization than are typically available from pharmaceutical companies.

InfoMed welcomes this progress in medicine which provides the physicians the advantage of finding the treatment therapy that is most effective for their patient even though it may only be needed by a small percentage of the population.

Is best we hear from the expert Mr. Mahendran, a senior pharmacist who has been compounding under Aurelia Pharma Sdn Bhd since 2011.

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InfoMed’s interview with Mahendran

InfoMed : How is the market penetration of CP and in which countries?

Mahendran: The resurgence of compounding pharmacies began around the mid-nineties, principally in Europe and the United States, out of a need to fill the gap for individualized or customized medication needs.  This was due to dosage adjustments required in some instances, where patients’ needs were either not being met by mass produced drugs, or that there were requirements to do away with some excipients in these drugs that were causing untoward reactions (i.e. adverse events).

However, development was initially slow, until the release of the Womens’ Health Initiative (WHI) Study in 2002, which reported on the outcomes of women who were on long-term hormonal replacement treatments, with synthetic hormones, showing an increased risk of cardiovascular disease, strokes and breast cancers.  This led people to seek alternative therapies, resulting in an increased need or demand for the bio-identical hormones, in place of the synthetic hormones.  Consequently, this assisted in the growth and development of compounding pharmacies to provide such services.  Hence, it is only quite recently that compounding pharmacies began to flourish.

However, it is pertinent to note that this is still quite at an early stage, as most compounding pharmacies are found in the US, Europe and in Australia.  As far as the rest of the world is concerned, there is still a dearth.  In Asia, compounding pharmacies are found in Thailand, Malaysia and Singapore, although the level of development is still slow.

InfoMed : Where does Malaysia stand in this respect?

Mahendran : in this region Malaysia is fairly advanced where this is concerned.  There are already a few pharmacists offering their professional services to make customized preparations for the benefit of Malaysians.

InfoMed : How do you ensure that the drugs made by compounding pharmacies are safe?

Mahendran : To answer this question, a lot really depends on the compounding pharmacy as well as the responsible compounding pharmacist.  The onus is on the pharmacist to ensure that all preparations coming out of his/her pharmacy are indeed quality focussed.  This is in regard to his professional training and knowledge of the medicaments being offered to the profession and the public at large.

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“At Aurelia Pharma, this is the topmost consideration, and to ensure this, we have a Quality Assurance programme in place, where random samples are taken, from prescriptions we receive, and sent for assay at an independent facility.  These have to conform to the British Pharmacopoeia specifications which we have adopted as our standard”

InfoMed : The important role played by CP for better patient care?

Mahendran : Compounding pharmacies play an important role for providing customized preparations for patients.  These could be for a product that is no longer commercially available, or one in which a specific ingredient has to be avoided owing to perhaps, an allergic reaction to that ingredient.  In other instances, it could be a situation where a specific preparation has to be made, where two or more ingredients may have to be mixed, for synergistic treatment effects or to ensure compliance on the part of the patient.

InfoMed : When will a patient need a compounded drug?

Mahendran : This is usually when a finished product is not commercially available.  An example would be for women who are in need of bio-identical hormones for the control of their menopausal symptoms.  Bio-identical hormones are those which have a chemical structure similar to the hormones naturally produced by the human body.  These preparations are not always available commercially; or even if they are, they may be in standard doses which may not be what the patient may require; being either in higher or lower doses.  Compounding allows the exact dose to be made available for that patient’s specific needs.

InfoMed : How is the formulation derived?

Mahendran : Formulations are derived from a Compendium of formulae of preparations or Reference Text.  Examples of these are the British Pharmacopoeia, the U.S Pharmacopoeia or the Martindale:  The Extra Pharmacopoeia.  These reference texts provide valuable information to the pharmacist on preparing medicaments, what doses to use, how to mix them and so forth.  They also provide the amounts of active ingredients that should be in a specific preparation.  Any deviation would render them failing to adhere to the standard, meaning they would fail from the quality perspective.

InfoMed : Who prescribes the drug made by CP?

Mahendran : Professionals who may prescribe drugs made by compounding pharmacies are doctors, dental surgeons and veterinarians.  They are typically the people who may use the services of compounding pharmacies.  In Malaysia, the predominant prescribers are doctors, who avail the services of compounding pharmacists to treat their patients.  Malaysian dental surgeons and veterinarians have still not used these services, although in the more developed countries, they form a significant group of prescribers.

InfoMed : Are adverse effects or reactions likely or possible?

Mahendran : Adverse events or effects are usually related to the chemical substance itself.   This occurs irrespective of whether the product is manufactured in a large-scale factory or produced in compounding pharmacy.  For this reason, the Ministry of Health Malaysia, advocates the reporting of all adverse events to the MADRAC (The Malaysian Adverse Drug Reactions Advisory Committee), in the interest of public safety.  Such reporting allows for information gathering on the safety of drugs in use.  Compounding pharmacies as well as doctors are also required to forward such information to MADRAC, in the event any of their compounded medications have resulted in any adverse event, whether causality is established or otherwise.

Besides the adverse events or reactions brought about the drug itself, there could be other reactions which may be related to the processes at the pharmacy itself.  These include factors revolving around cleanliness or contamination, which may be avoided by having Standard Operating Procedures (SOPs) in place.

A compounding pharmacy which has SOPs in place, will avoid risking products to cross-contamination and quality issues.

InfoMed : When can things go wrong in the formulation?

Mahendran : Things that can go wrong in the formulation usually arise from the lack of knowledge of the physical, chemical or pharmacological properties of the ingredients, active or inert.  Physical and chemical properties may result in a product being unstable and breaking down, even before it’s shelf-life is over.  Examples of these are phase separation of an emulsion or the caking of a suspension due to ingredient incompatibility.

Pharmacological incompatibility is a consequence of mixing two or more ingredients which have antagonistic pharmacological properties.  An example is the combination of estrogen and progesterone in a single cream preparation.

InfoMed : Is this the direction towards personalised medicine?

Mahendran : Generally speaking, compounding pharmacies yield medicinal products which are actually geared towards personalised medicine.  As previously mentioned, these are products tailor-made to the specific requirements of that individual patient.  This is in exact opposite to commercially available products, where the “one-dose-fits-all” is the nature of the product.  What this results in, is that in some patients this may be too high a dose, leading to adverse events reported in them, or to too low a dose in some others, with no clinical impact seen at all.

InfoMed : How about the cost implication considering the high price of commercial pharmaceutical drugs?

Mahendran : Commercially available preparations are made by large-scale mass manufacturers, either the originator companies which are the research-based multinationals (MNCs) or the local producers who manufacture off-patented medicinals.

Much of the high price pharmaceuticals are for products belonging to the MNCs, who have absolute protection for their patented products, during the patent period.  These are in some way justified from the perspective of the MNCs, as they have to recoup the high development costs involved, before the product makes it to the marketplace, while recoup periods have substantially reduced compared to the yesteryears.

Compounding pharmacy products are based on the likes of off-patent substances, or raw materials of bio-identical hormones which cannot be patented, under international law.  Since they are not patented, there is no protection and free-market forces dictate the final pricing of such products.  Therefore, competition keeps prices of compounded products at an affordable level.

InfoMed : What does the future holds for CP, especially in patient care?

Mahendran : I think the future is quite bright for CPs, as there is a trend towards personalised medicine, as can be seen in The United States, Europe and Australia.  Furthermore, the holistic medicine approach is gaining traction in the country, where there is a trend currently to take the preventive approach to medical management of patients.

InfoMed : Who regulates CP in Malaysia?

Mahendran : Compounding pharmacy operations are regulated by the Ministry of Health, Malaysia.    All Compounding Pharmacies require the services of a registered pharmacist, under the Registration of Pharmacists’ Act and must be licenced under the Poisons Act.  These are the two principal Acts that apply to CP operations.

To ensure compliance with the law, Compounding Pharmacies are inspected by the Ministry of Health on an annual basis.