The Drug Regulatory Authority of Pakistan (Drap) recently directed all provincial governments to ensure that doctors in public and private healthcare facilities prescribe medicines only with their generic names.

The Drap's notification came in response to public outcry over a common malpractice in the country where pharmaceutical companies are accused of offering financial incentives to encourage medical practitioners to favour a particular brand.

We welcome the new regulations that were issued ostensibly to reduce the public's out-of-pocket expenditure on medicines by increasing public access to low-cost generic drugs. The Drap has also recently sought stakeholders' opinions on the registration of generic medicines.

In this article, we highlight the pitfalls of the newly proposed generic prescribing regulations, which if left unaddressed, can jeopardise the foreseen benefits.

What's in a name?

Most medicines have an international non-proprietary name, referred to as the ‘generic name’ and a brand name that is proprietary to the pharmaceutical company producing them.

For example, ‘paracetamol’ is the generic name for the medicine present in the two famous branded products, Calpol and Panadol. Consumers and prescribers both have different preferences for a brand. For instance, some readers of this article may be partial to Calpol, while others may prefer Panadol or even locally produced brands of paracetamol in their region.

Much like brands in the consumer goods industry, branded medicines are often expensive and have a perceived impression of better quality among consumers and prescribers. The question is whether branded medicines are any better than the cheaper generics or is it just the consumer or prescriber’s perception?

To bring this into perspective, one needs to understand how medicines are developed.

The innovator companies invest millions in drug discovery to bring new molecules from the laboratory and animal testing through to the clinical trials.

It usually takes around 10 years to get a new drug to the market and costs millions of dollars to meet the toughest safety and efficacy standards imposed by drug regulatory authorities.

A stark reality is that the majority of new drugs and molecules fail during their journey and never make it to the market. This highly risky investment in pharmaceuticals rarely produces a successful candidate that makes it to the market.

The new medicine, which is able to meet all the rigorous standards, then becomes the intellectual property of the innovator company, which in turn enjoys the sole right to manufacture and sell the new drug throughout its patent life — lasting for around 20 years.

To protect the return in investments, drugs are often patented very early on in the discovery stage. Hence, by the time a product is launched in the market, there is often a fraction of the patent life left for the company to get a return on their extensive research costs.

Once patents have expired, other companies can start producing the same product, often referred to as low-cost generics. The drug regulatory authorities ensure that these low-cost alternatives meet the same quality standards as the innovator’s product. The price of these generics is much lower than the innovator’s product, as these generic manufacturers do not invent new drugs and costs are mainly attributed to standard manufacturing operations.

So if branded medicines are expensive and generic products can provide a low-cost alternative to innovator brands, thereby reducing the out-of-pocket public expenditure on medicines, it should make sense that the Drap is encouraging the prescription of medicines by their generic names.

It is also true that in many countries, for instance the United Kingdom, generic prescriptions are a norm in general medical practice. However, there are serious issues that need to be considered when it comes to enforcing these regulations in Pakistan.

1. Regulatory control

All low-cost generics must demonstrate that their product is equivalent to the innovator’s product in its quality and efficacy, often demonstrated by ‘bioequivalence’ studies.

Regulatory authorities such as UK’s Medicines and Healthcare products Regulatory Agency (MHRA) and European Medicines Agency, or the United States Food and Drug Administration (FDA) issues marketing authorisation for generic products in their respective markets after vigorous scrutiny of the products' quality and efficacy.

In Pakistan, like many low-middle-income countries, the generic products are approved without demonstrating bioequivalence or going through the tight scrutiny that generic medicinal products have to go through to get access to western markets.

2. Potent drugs

Potent drugs are medically termed as ‘narrow therapeutic index drugs’. These medicines are biologically effective at a very small dose, such as in micrograms, and require a very tight control of dose uniformity to maintain efficacy and prevent drug induced toxicity. Some examples include psychoactive and cytotoxic drugs, steroids, chemotherapeutics etc.

Subtle changes in formulation and manufacturing methods may results in significant changes in product performance and safety of these substances. Generic products must meet a higher level of standards to ensure the efficacy and safety is at par with the innovator’s product. The drug regulatory authority in Pakistan, like various other developing countries, has not been able to enforce these standards yet.

3. Release technology

Some pharmaceutical products use proprietary formulation strategies to optimise the release of the medicinal agent — the substance with medicinal properties that is used to treat and cure an illness — from the product.

These products are often referred to as ‘modified release’ (MR), ‘sustained release’(SR), ‘controlled release’(CR), ‘extended release’ (ER), or ‘timed-release’ products. These can be formulated as tablets or even injections.

In contrast to conventional products where the medicine is released immediately upon administration of the product, the release of medicinal ingredient is controlled over an extended period of time in these products using specialised formulation technologies.

The efficacy and safety of these products, therefore, mainly relies on proprietary formulae (trade secrets) of the manufacturer. These products are unique in their characteristics and once patients are maintained on a particular product, it is not advised to switch to another product unless inevitable, for instance, product discontinuation or shortage of supply.

The switch to a different product, however, requires close monitoring, often requires adjustment of dosing schedules, and may lead to lack of tolerability, poor compliance, or adverse drug reactions.

These products are always prescribed with their brand names to ensure consistency in prescribing and dispensing for a patient. The generic copies of these products are also branded, and low-cost alternatives are also prescribed with their brand names as they cannot be ‘exactly the same’ as the innovator’s product to ensure consistency and patients’ safety.

4. Biological products

Biological products such as insulin vary significantly in their proprietary formulation and different insulin products may vary in terms of the rate and extent of insulin release from the injection site and consequent differences in blood sugar maintenance over a 24-hour period.

It takes a lot of hard work for diabetologists and specialist diabetes nurses to monitor a new diabetic patient starting on insulin products to optimise the desired combination of immediately acting and prolonged-acting insulin formulations to personalise a dose for a patient.

Once a patient is settled on a dose combination of insulin, the prescribers stick to the same branded combinations to ensure safety and compliance.

Unsolicited changes in such products are not safe and can lead to life threatening hypoglycaemic conditions. The approval process for the low-cost alternatives of the innovator’s biological products undergoes a much higher level of scrutiny under ‘biosimilar’ regulations before they are approved in western markets. The low-cost generic copies of biological products are also branded and are prescribed with their brand names to ensure consistency in clinical response and patients' safety.

5. Medical devices

Some medical devices must always be prescribed by brands. One such example is inhalers for respiratory diseases. Inhalers are very specialised and precisely engineered medical devices that uses proprietary engineered techniques to aerosolise very fine droplets or particles of the drugs for delivery into the airways.

There is a huge variation in the emitted dose between different products, device resistance and lung capacity of the patient. The selection of an appropriate inhaler requires a lot of effort from practitioners to ensure that product selection is personalised to the patient's need and patients are tutored on the inhaler technique by specialist respiratory nurses; the inhalation technique also varies between different brands of the inhalers.

Once a patient is maintained on a particular type of inhalers, both the prescriber and pharmacist ensure that the patient is always supplied with a similar device to ensure safety and compliance.

Therefore, specialised medical devices, such as inhalers are also prescribed either with their brand names or extended generic names that are followed by the inhalation device type descriptors to ensure patients safety and compliance.

6. 'Poly pills'

Some pharmaceutical products contain more than one medicinal agent, often referred to as combination products or ‘poly pills’. Common examples include products for diabetes, hypertension and combination therapies for infectious diseases such as tuberculosis.

Often some patients with chronic illnesses, such as diabetes and hypertension, must take several medicines in a day that often leads to poor adherence and compliance. Poly pills often address this problem and reduce the number of tablets or capsules.

These poly pills contain a unique combination of medicines and dosages. They are, therefore, usually prescribed by their brand names to reduce dispensing errors and ensure safety and compliance. Multivitamin products are another example and the range of vitamin and mineral combinations and dosages that are available in the market varies significantly.

7. Over-the-counter consumer products

Not all medicines need a prescription; some products are legally permitted to be sold over the counter without a prescription. Often, branding is inevitable for these consumer products used for minor ailments, such as cough and cold or general-purpose pain relief medications. The branding ensures that all advertising and marketing efforts by a pharmaceutical company can influence the prescriber or consumer's decision towards a particular product.

These products are often advertised in television, print or social media to influence consumer behaviour. Often, branding also helps consumers select the product that meets their personal taste for better concordance and compliance, for instance, speciality formulated products to improve taste and palatability, size and shape of dosage forms, choice of flavours etc.

8. Locally designed brands

It is important to understand that all branded medicinal products in Pakistan are not innovators' brands. All local generic products are also branded in Pakistan with proprietary trade names.

The irony of the fact is that locally branded products in Pakistan are not always cheaper than the innovator’s brands available in the Pakistani market. This discrepancy is due to a very tightly regulated medicines pricing structure in Pakistan.

Many innovators’ brands were registered decades ago and were registered with retail prices calculated based on the then manufacturing costs (material, labour, utilities etc).

The prices are not revised regularly on the retail price index, contrary to the retail prices for general consumer goods that usually increase with inflation on a regular basis.

The registered price for a recently registered generic product (a copy of the innovator’s brand registered many years ago) will be based on the current manufacturing costs and therefore often registered and sold at an equal or even higher retail price than the innovator's brand.

This means that the new law enforcing generic prescriptions may not necessarily reduce the out-of-pocket medicine expenditure by the patient.

9. The fault in our medical stores

Medical stores in Pakistan are unlike community pharmacies in the United Kingdom that are run by qualified pharmacists. The majority of medical stores in Pakistan are run by unqualified non-pharmacists, often educated not beyond a secondary school certificate.

A new law enforcing generic prescriptions may put patients at the mercy of those shopkeepers who may only stock products that favour a higher profit margin for their business. It is very unlikely that these savings will be passed on to the end consumers; this potentially also opens the doors for unwarranted monetary incentives towards distributors and retailers to manipulate the supply chain in favour of particular products.

This will also put patients at risk of receiving inappropriate products, in particular, when we know that many products are not truly equivalent to each other (the absence of bioequivalence regulations). This may risk patient safety for cases like potent drugs, modified-release products, medical devices and poly-pills as explained earlier.

10. The ethical dilemma

The core of the problem is poor ethics in the medical practice combined with a poor enforcement of antibribery regulations in Pakistan, where some pharmaceutical organisations solely rely on monetary incentives for medical practitioners in order to get their products prescribed.

These incentives incudes a range of perks and discounts, free gits, foreign holidays, luxury residential and office refurbishments, and even direct cash incentives.

The pharmaceutical companies have huge marketing budgets which they are legally allowed to spend on sales promotion activities. Some good practice examples include promoting health education among the public, health screening, public health promotion activities, medical education and supporting medical research, among others.

Often, the majority of pharmaceutical companies in Pakistan find it difficult to compete in a very crowded generics market, in particular when they don't invest in innovative products.

It then becomes very difficult for pharmaceutical companies to convince prescribers on scientific grounds to favour a particular product in their medical practice. This is when the bribery and financial incentives help in gaining a market share to achieve sales targets.

The ethical and regulatory dynamics in the developing world are rapidly changing. The poor practices often perceived acceptable in the developing world today may no longer be acceptable tomorrow.

In 2014, the CEO of a large pharmaceutical company was deported from China after pleading guilty of bribing doctors to prescribe its products. The pharmaceutical company was also fined millions of British pounds as a penalty for their illegal practices for sales promotion in China.

Ethical considerations in Pakistan

The new regulations on ethical marketing, notified earlier this month, are the first step in Pakistan to legally enforce ethical marketing to healthcare professionals.

Ethics in professional practice should be the fundamental part of medical and pharmacy education. The doctors and medical associations in Pakistan should seriously reflect and address the current biases in prescribing practices.

Healthcare professionals must also actively encourage pharmaceutical companies to spend their marketing budgets on healthcare education and medical research that will promote the development of bespoke innovative medical and surgical products tailoured to the needs of patients in Pakistan.

These funds can also be utilised in understanding disease dynamics in Pakistani society, for instance infectious diseases, antimicrobial resistance and emerging superbugs, diabetes and cardiovascular conditions which currently constitute the biggest healthcare burden on Pakistani society.

We welcome the new generic prescribing initiative from the Drug Regulatory Authority of Pakistan, albeit it cannot be ruled out that the risks of bribery and corruption may shift towards the pharmaceutical distributors and medical suppliers.

In the absence of fully appreciating the underpinning science of drug discovery and regulatory compliance, the full benefits of the new prescribing regulations may never be achieved.

A similar attempt was made in the past through ‘The Drugs (Generic Names) Act in 1972’ and ‘The Drugs Act 1976’ in Pakistan, but it failed to achieve its objectives.

The national policy for drug registration, pricing, and bioequivalence regulations are the key building blocks for establishing the necessary infrastructure for successful implementation of the generic prescribing regulations in Pakistan.

Ethics, regulatory compliance, and better governance are the key to success!

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Dr Hamid A Merchant (@HamidMerchant) is Subject Lead in Pharmacy at the University of Huddersfield, UK

Dr Izhar M Hussain (@DrIzharHussain2) is the Director of the Institute of Business & Health Management (IBHM) at the Dow University of Health Sciences (DUHS), Karachi, Pakistan.

Both authors have extensive work experience in academia and the pharmaceutical industry. They have not received any funding to commission or support this work.